Family and Allies
Leonardo: Out of all the Turtles, Leo is the one Karai is closest with and is the first of the Turtles that she meets. While she attacks and fights with him often, she never does him any serious harm and just enjoys sparring with a worthy opponent. Leonardo, in turn, was both confused by and attracted to Karai (as shown in New Girl In Town). She is dangerous, but Leo believed that there was some good in her but she betrayed him. She seems to be deceitful and manipulative in The Alien Agenda, using Leo's feelings for her against him, especially in his time of need. In Enemy of My Enemy, she returns, seeking information about the Kraang from the turtles. This time, instead of wanting to fight the turtles, she decides to make a truce with the turtles in order to defeat the Kraang ship. She goes against the Shredder's orders because she knows they'll all die if they don't set aside their differences and take down the ship. At first, the turtles, mainly Leo, are very skeptical of her and decline her request for a truce, but after she leads it away from the Shellraiser, they comply. Because Leo saved her and allowed her to speak to all of Turtles, Karai develops some friendship for him.
However, because he and his brothers tried to attack her father Shredder, the truce was called off and her trust in him was left now uncertain. Now she's vengeful towards the turtles and is willing to do whatever it takes to take them down. It was revealed in the Season 1 finale that Karai is Splinter's lost daughter (Miwa), who was raised by the Shredder. Leo seems more aggravated with Karai as she wants to hurt him and his loved ones more often, he tells her that her vendetta is with him not his family. In Follow The Leader Splinter told Leo that Karai is his daughter. In Wormquake Leo tried to tell her the truth but she didn't believe him. But during the end she over hears the group talking about her being Splinters real child and she looked guilty and sorry for herself. During The Wrath of Tiger Claw she began changing her ways and soon was talking to April before Donnie and Leo came. She told them that she believed Leo and right away Leo brings her to the lair where Raph, Donnie and Leo start a fight with Leo and Donnie deafening her. After finding out the truth she tells them she was leading Tiger Claw to them. After the fight Tiger Claw gave her the honor to kill Leo but she then fought Tiger Claw instead but got knocked unconscious. Tiger Claw ran off with her and Leo wanted to help but Mikey was badly hurt so they had to leave. When the turtles find shredder helmet in The Legend of the Kuro Kabuto Leo wanted to make a trade with Shredder which was Shredder's helmet for Karai. In Vengeance is Mine Leo was willing to go behind Splinters back in order to save Karai. When they save her and brought her back Leo blushed when Mikey embarrasses Leo in front of Karai. As Karai tried to sneak out to go attack Shredder Leo said he wanted to come even tho she said no so she walked up to him and looked like she was going to kiss him but only got close so she could throw blinding gas in his face and then runs off. As Leo jumped up onto Karai cage to free her Shredder cuts the cage by mistake and Karai is then Mutated. She runs out of the building and Leo tries to stop her but she is gone already and blames himself for what happened to Karai. It is shown that he still has feelings for her and Karai seem to be hiding her feelings but now there is no clue if she can still remember who his is due to her mutation. In Serpent Hunt when Leo tries talking to her Karai can't understand and Donnie says that every minute she becoming like a snake, but Leo doesn't give up. Then it looks like Karai about to attack him but comes eye to eye with him and says his name she then turns into her human form and begs for help. Leo offers to take her back to the lair but she says that she's too dangerous. Later on during the battle with the turtles, Shredder and Ivan Leo breaks Karai free and tells her to leave before they can catch her again. She then points east and says "Comet" giving Leo a hint where she could be, but it turned out to be a hint to a place where she could say "goodbye". Later on the fourth season and into the fifth season Karai finally decided to really ask for help and was seen with Leo and his team more often than before.
Raphael: Raph is the second of the Turtles that Karai meets, and Raph is the first to find out about Leonardo's "friendship" with her. Unlike his brother, Raphael immediately distrusts her. He tries to warn Leo that she is the enemy and not to trust her. He still does not trust her when she wants to help defeat the Kraang and came up with the idea of setting a trap for Shredder and (like the rest of his brothers) attempted to assassinate the Shredder to annoy her. Though Karai is actually Splinter's daughter, it didn't matter to him whether this distrust is a family feud or not, even if Leo still cares about her. But as the series progressed, his distrust for Karai faded.
Donatello: Donnie does not know too much about her mainly because Leo never mentioned her until after they revealed her in The Worldwide Genome Project headquarters. Based on Donnie’s observations of her, he does not like her because of her need to cause trouble and was part of the Foot Clan. He is wary of Karai's tactics and does not trust her at all, not even when she offerd to help him and his brothers fight the Kraang. As the series progressed Donnie started to trust her. Donnie also was a part of the attempted assassination of the Shredder. In Broken Foot, Karai feels bad for Donnie being hurt as the explosives she planted on the Auman Chemicals Factory exploded as the purple masked turtle was trying to save Raph and Mikey. Revealing that she also cares about him.
Michelangelo: Mikey also did not trust her and was surprised that Leo trusted her. When she wanted to help fight the Kraang, Mikey was wary of her. Mikey also participated in the attempted assassination. They see her as an enemy working for the Foot, but she sees them more as play toys for her amusement. In Booyaka-Showdown, it is revealed that Karai is Splinter's daughter, Miwa, who the Shredder took and raised her as his own daughter after the events of their final battle. When Splinter told the turtles about this, they were all shocked and Mikey questions about Karai being their "sister".
April O'Neil: April is the first female human that she has met in the whole series. Based on their brief encounter in "Karai's Vendetta", they seem to have quite a lot in common. They both know how to speak Japanese, they both know how to drive a motorized vehicle, they're both kunoichis (except Karai has better Martial Art skills), they are both the romantic "interests" of two of four Turtles, and both of their biological fathers have been mutated into animals (both of which are mammals - A rat and a bat). They seem to become enemies in "Karai's Vendetta" (though Karai does seem to have a regretful expression on her face not very long after she attacks April). It is also suggested that Karai dislikes April somewhat and is jealous of her, due to the fact that she is very special and important to the Kraang and Splinter (a value that Karai doesn't think she has). At the very end of this episode, however, Karai appears to show signs of empathy and feeling slightly sorry for April when the other girl mentions that she lost her mother. If they weren't on different sides, it's likely that the two could be very good friends, and yet April probably hoped it would be that way and may have shon the same signs of pity when she learned that Karai is Splinter's very daughter, and their current views of each other have changed now that Karai has found out and accepted it. She chased down April to just talk to her instead of fighting. She then opened up to her about everything that was happening, Splinter possibly being her real father, Shredder lying to her for her whole life and where her loyalties lied, and her possibly betraying the Shredder which surprised April. They are then seen enjoying each other's company as they had a conversation until Leo and Donnie arrived. April also defended her by telling the turtles to stop in their tracks and to listen to what karai had to say. she then said that she believed Karai about believing Leonardo and what he said about Splinter showing that April trusts her now.
Casey Jones: Karai might have love interest with Casey. In The Deadly Venom, she was mind-controlled into confronting him, poisoning Casey when she bit him in the lip.
Tang Shen: Karai is Tang Shen's daughter, along with Master Splinter's. When she was an infant, her mother perished at the hands of Shredder when she intercepted a blow meant for Splinter, and was taken in by him. He then raised Karai as his own child and fed her countless lies about how her mother died and who committed the act. Karai has known this false truth for a big portion of her life, but when Splinter showed up in Shredder's hideout in "Booyaka-Showdown", her true feelings on the situation are exacerbated even more - and she now desperately hopes to avenge her own mother's death by killing her true father.
Even though she doesn't know what her mother was actually like, she carries a torn-off, dilapidated photo of her mother around with her. It is likely that this was part of a grander, family photo like the one Splinter has in the lair, but the Shredder probably ripped Tang Shen's part off to conceal his own lie.
Master Splinter: Karai is none other than Splinter's biological daughter. In the episode "Booyaka-Showdown Part 2", Splinter discovers this after the Shredder reveals to him that he took his daughter, Miwa, away and raised her as his very own child. When Karai soon shows up, he is then able to turn Splinter's own daughter against him by using what he had formerly told her about whom killed her mother, Tang Shen. She then tries to fight Yoshi, but her manages to avoid her attacks and escapes. She then demands to know why he won't fight with her and calls him a coward. He then leaves, heartbroken at what the Shredder has done to his daughter. In "Follow The Leader", she demonstrates how truly spiteful and vengeful she has now become towards him. She hates him to the point where she wanted to kill the Turtles before his very eyes and ruin his life in so many more ways. When she successfully tranquilizes Splinter in "The Manhattan Project, Part 1", she seems to view this as a big victory and she also even appears to draw some sadistic pleasure from doing this. It is very clear that Splinter knows that his daughter is fully alive, active, and working alongside the Shredder, In The Manhattan project, part 2, she over hears splinter talking to the team about him being her biological father and whether if she will figure it out and accept it is her decision. She then has a guilty expression on her face suggesting that she's starting to question herself and everything else. In The Wrath of Tiger Claw her knowledge of the truth caused all her hatred of him to disappear and after her rescue in Vengeance is mine she hugged him for the first time. After her mutation into a snake-like creature, her love for him gave herself the strength to fight her new instincts and not devour him. When Splinter was seen drowning at the ending of The Invasion, Part 2, she quickly swims towards her father to save him. Before leaving, she touches him with her nose to his face.
Shinigami: Shinigami is Karai's old friend from Japan who is quite close and loyal to her, she seems to take orders from her without arguing or hesitation. When Karai wanted to rebuild the the Foot Clan in a more honerable way, Shinigami came to New York to help her in fighting Shredder and his criminal empire. In The Super Shredder Shinigami told the mutated Shredder that he was a monster and that she was going to destroy him for everything he did to Karai. After the fight the Shredder got Karai to surrender by telling her that if she resisted, he would hunt down and kill Shinigami.
Enemies
The Kraang: When Karai discovers the Kraang fighting the Turtles and understands their responsibility for the Turtle's mutations and their invasion scheme, she tries to explain it to Shredder but he remains unconvinced of why he should be interested in them and their possible use to his vendetta against the Turtles until he finds their technology (including mutagen) useful and finds out that they are hunting the Turtles as well due to the danger they pose to the Kraang's invasion and their guardsmanship over April O'Neil (who is a use to their conspiracy due to her being the perfect human-Kraang mutant that they made her into before she was born).
Shredder: Karai's former relationship with her false father was actually quite complicated. She seems to fear The Shredder at certain times, just like Bradford and Montes do, yet she obeys him, but she doesn't appear to respect him as much. It is possible that she wants him to respect her equally, such as when she mentions The Kraang and shows him the droid she had picked up, attempting to intrigue him somehow. In Enemy of My Enemy, just a little more insight is given into Karai's relationship with her Shredder. Karai saves him a total of two times in this very episode. She tackles him out of the way to prevent him from getting zapped by an electro-grenade and bravely jumps into the sea to save Shredder from drowning towards the end of the episode.This proves that Karai truly loved Shredder as her father despite constantly disobeying his orders.That all changed when she finds out that Saki is not her true father, she betrays him and he has her locked away in his lair's dungeon, after that event she began to hate him for lying to her for her entire life. In Vengeance is Mine she learned that it was Shredder responsible for her mother's death and how he kidnapped her and she wanted revenge, even after her real father told her that "revenge only leads to more pain”.
Rahzar and Fishface: Karai's relationship with Bradford and Montes is vastly unknown for the most part, but she does seem to stand up for both in a way, even when she told the Shredder that they got mutated when she wanted Shredder to try and help her figure out what was going on with the Kraang.
Stockman-Fly: Karai was a good help for Stockman when he was struggling with his inventions for Shredder, so she provided him with Kraang components to reverse engineer the machines with.
Tiger Claw: At the moment Karai and Tiger Claw first met, they did not like each other. All of the other members of Shredder's forces seem to be rather stunned to see such a menacing looking man beast, while Karai coldly asks why The Shredder has enlisted yet another freak. Right afterward, Tiger Claw tells the Shredder that he is quite disappointed that this is the Foot Clan he told him all about. Karai continues to show no respect by teasing him about losing his tail. She was angered by the fact that Shredder made tiger claw his second-in-command instead of her, but was willing to work with him until she finally accepted the fact that Splinter was her real father and betray him and the Shredder.
Bebop and Rocksteady: Karai probably dislikes Zeck and Steranko because they were hunting her, for they planned to use her as a bargaining chip for Shredder in exchange for a way out of the Kraang-invaded city.