Friends and Family
All of the Turtles: Leo is the leader of his brothers. And he likes to be the one on the team who is not afraid of anything. That's why Raph refers to him as "fearless leader" sometimes. Leo is very protective of his younger siblings, and doesn't want anything to happen to them. As shown in the last episode of season one, Leonardo would even risk his life to save his brothers.
Master Splinter: Leo loves to train, spar, and learn more about ninjutsu. He likes to train with his sensei, and father; Master Splinter. Splinter taught him everything he knows about ninjutsu, and Leo respects him very much. Out of all the turtles, Leo has the closest relationship with his father, very often going to him for advice. Like his brothers, Leo is very protective of his father as well. Leo was the first turtle to call Splinter father in a long time.
Raphael: Leo and Raph seem to always be fighting, as seen in some previous episodes, the two brothers really care for each other. Leo will do anything to protect Raph, as Raph will do anything to protect Leo. They will even risk their lives for each others saftey. As seen in The New Girl In Town, Raph thinks that he should be the leader, considering that he's the strongest out of the four turtles. But however, Leo thinks otherwise. Leo doesn't believe that Raph doesn't have what it takes to be the leader. But as explained, they both care very much for each other. In the first finale episode of season one Leo tells his brothers to run out of TCRI for he was going to blow it up. As Leo was falling Raph catches him. In the second finale episode Leo holds the Kraang leader back while the other escaped but Raph refused and tried to help but Mikey and Donnie hold him back and as they escape in the pod Raph say "Leonardo!" and as the pod floats in the water, Raph says that he was too hard on Leo and if he had a second chance he would be nicer, but was relieved when Leo revealed himself alive. This is almost true, however, when Raph sometimes criticizes him and his brothers after Slash's sudden betrayal, but this eventually changed when Casey came and was introduced by April to the entire team and Leo was pretty glad to how much of Raph's criticism softens even with Casey or the redeemed Slash around. Raph's dislike for Karai, however, doesn't change much for Leo and Raph eventually points that just because she is really their half-sister doesn't mean trusting her is an option, even with wanting her to except the truth about her past.
Donatello: Leo and Donnie don't really fight often, in fact, they get along pretty well. But in the last episode of season two, they disagree on some things. For example: In The Invasion, Leo suggested that they should get out of the city before the Kraang Invasion got even worse. But, Donnie thought that they could take the turtle mech that Donnie had been working on and defeat the Kraang and the Invasion would be over. They fought on and off about the situation, throughout the episode. But other than that, they get along pretty good.
Michelangelo: Leo and Mikey don't talk to each other that often, but they still have a really good relationship with each other. In the episode Mazes & Mutants, Leo and Mikey worked together to come up with the game, L.A.R.P. And in the first episode of season three, when Leo finally woke up, Mikey gave him a hug and animated tears of joy came out from his eyes. Even though they don't often show it, they will always love each other no matter what comes their way. In The Pig and the Rhino Mikey begs Leo to go to the Comet Roller Coaster to find Karai. Leo grants his request and decides that he wants to go with him. The two of them work together to save their brothers and human friends from Bebop and Rocksteady. In Attack of the Mega Shredder Leo went back Mikey in an attempt to slash it open but fails and nearly got eaten himself, he looked at Mikey's Grappling Hook and gave a sad look believing he was deceased.
Karai: Leonardo is the first of the Turtles that Karai 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 The 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 the Kraang Scou Ship 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, 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. During The Wrath of Tiger Claw, she started to act different and soon was talking to April before Donnie and Leo came. She told then that she believed Leo and right away Leo brings her to the lair where Raph and Leo start a fight with Leo defending her. After finding out the truth that Splinter is her father, 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's 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 ughshe 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 is becoming more snake like 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 Steranko, 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.
As the series progresses, Leo and Karai start to have a romantic relationship, which is seen in When Worlds Collide.
April O'Neil: Leo and April barely talk to each other, but they are still friends. As seen in the "New Girl In Town", Leo went to April's house to tell her about how had met Karai that night. Once Leo told her that Karai was part of the Foot Clan, April pulled out a newspaper and slapped him. And she kept yelling at him, about how he shouldn't be hanging out with her, because she's in the Foot Clan, but her view of this changes long after when she learns that Karai was Splinter's very daughter. So, come to think of it every time they talk to each other, they end up fighting. But they don't talk to each other often, so that means that they don't fight that much.
Casey Jones: Just like April, Leo and Casey don't communicate that often. But in the episode, A Foot Too Big, Leo and Casey were the barn laughing together about the jokes they were making about Bigfoot. And in The Invasion, April, Donnie, Raph, and Mikey, went down to the sewers to look for sensei, while Casey stayed with Leo in the van went out to look for his family. But, Leo was unconsious so he has no memory of when that had happened.
Enemies
Shredder: Out of all of the turtles, Leonardo has had the most interactions with Shredder; each of them highly antagonistic and adversarial. In Wormquake!, Shredder taunts him to watch Splinter die when he had Tiger Claw capture and poison the ninjitsu master, also telling him that it will be the last fight he ever sees. In The Legend of the Kuro Kabuto, Leo made a deal with Shredder involving the exchanging of Karai (which turned out to be a bomb) for the Kuro Kabuto, but Shredder attacks him, refusing to let the young ninja leave without a fight. In The Invasion, when Shredder learns that Leo has been separated from his brothers, Shredder tracks him down and sends Foot-bots after him, sadistically wanting to "see him suffer" before killing him. During this time, he claims that Leo is foolish and overconfident due to his youth. When Leo defeats all of Shredder's lieutenants, Shredder himself knocks him unconscious and has him taken away. In Serpent Hunt, Leo briefly argues with Shredder about his "parentage" over Karai. Recently, in Casey Jones VS. The Underworld, as Leo engages Shredder in another ferocious battle at the Auman Chemicals factory, he claims that he is going to end Shredder once and for all. Because of this, Shredder may despise Leo more than any of the other turtles while Leo may show the greatest amount of disdain for Shredder compared to all of his other enemies.
Tiger Claw: Since the villain's first appearance in The Manhattan Project, Leo has frequently encountered Tiger Claw and engaged him in combat both with and without his brothers. In The Manhattan Project, Leo was pinned from behind by Tiger Claw when he tried to rescue Splinter and before he attempted to draw his weapons on Shredder, only to escape his grip due to the arrival of Raphael and Michelangelo. That same episode, Leo briefly fought with Tiger Claw (even managing to surprise him with a hidden weapon in one of his Katana) and managed to kick him away from Splinter when he had the superior ninja master pinned. In The Wrath of Tiger Claw, after Leo was defeated along with his brothers, Tiger Claw planned to finish him off first, but was willing to let Karai do it instead. In The Invasion, though tired and weakened from fighting Kraang and Foot Bots, Leo engaged Tiger Claw (along with Rahzar and Fishface) and actually managed to defeat him with one kick.
Stockman-Fly: Leo tends to forget Stockman's name (examples: "Dexter Backsman", "Daxter Boxman", "Blister Speckboy", etc.)
Fungus Humungous: Leo proved highly susceptible to the spores of Fungus Humungous, which brought out his fear of failing his team as a leader. Despite this fear, he faced it and defeated the villain by exposing it to sunlight.