Takeshi thinks Tsuna is amazing and treats him as a very close friend after the latter saved his life. Although he is rather naive towards what is really happening during the series, Takeshi is very devoted and loyal to Tsuna. He fights for him, protecting him above all else. His protective sense to Tsuna was first hinted in the manga when Takeshi declared that he will be Tsuna's Right Hand Man while Gokudera will just be the ear lobe. In the Future Arc, Takeshi showed great distress at not being able to beat Deisy in the Choice battle, thinking that he had somehow disappointed Tsuna and the Guardians. He was also upset about losing to Ugetsu Asari during the Primo Family Arc, and silently apologized for making Tsuna worry. However, thanks to Tsuna, he managed to let go of this distress during the second trial of the Guardian Inheritance Test.
Takeshi thinks of Gokudera as a friend and although Gokudera does not seem to admit this fact, he also thinks of Takeshi as a trusted ally. However, there seems to be somewhat of a one-sided rivalry going on. Gokudera believes Takeshi is trying to become Tsuna's right hand man, when in reality, he is simply being his clueless self and enjoying their competitions. They therefore push each other to do their best and become stronger because of each other. Gokudera also enjoys calling Takeshi a "baseball freak" whenever he is acting laid-back in a tough situation, when he references something to baseball, or when he does not know something.
In the future, the present Takeshi scolds Gokudera for his coldness towards him. He says that he has no right to be Tsuna's right hand man right now, as the right hand man's job is to gather and unite the Guardians, not turn away from them. He goes back to being happy once Gokudera chooses to accept him.
Reborn is the one who "found" Takeshi and consequently made him join the Vongola. He has very high expectations of Takeshi's talents and eventually becomes his tutor in the Future Arc. Reborn says that Takeshi is a natural-born hitman. Takeshi, on the other hand, thinks that Reborn is an infant who likes to play with very advanced toys such as guns and bombs. After training with Reborn, he has acknowledged him as being powerful and is interested in hearing his secrets, which Reborn revealed to him after their training. Reborn seems to like sitting on Takeshi's shoulder.
Squalo is the first opponent Takeshi faced who uses a sword. After a humiliating defeat at Squalo's hands Takeshi trained extremely hard to learn the Shigure Souen Style in hopes of beating Squalo. Squalo can be seen as the oil that strengthened Takeshi's desire to become stronger and his rival at swordsmanship. After defeating Squalo in the Rain battle Squalo says that Takeshi has what it takes to become a great Swordsman, acknowledging him. He, like Reborn, also has high hopes for Takeshi. In the Future Arc, Squalo sends Reborn and Takeshi a video of the 101 battles he won in order to become the Sword Emperor, helping Takeshi and refiring his determination. In the Future Arc, it is also mentioned that Vongola has two Swords masters; one of which is Takeshi, the other Squalo. Squalo seems to get irritated at Takeshi as he chooses baseball over swordsmanship. Squalo is one of the few who notice that Takeshi is not at the inheritance ceremony and that he is an illusion, signifying that Squalo has gotten to know Takeshi behavior wise along with his capabilities as a swordsman. Squalo calls Takeshi a naive brat and yells at him quite frequently, but Takeshi doesn't seem to mind and they otherwise get along well.
Unlike others who were afraid of him because of his appearance, Takeshi treats Kaoru nicely and already regard him as his friend, being the only one who helps him when it comes to baseball and to the point that he saved him from Demon Spade's killing blow and forgave Kaoru even though he had nearly killed him. Kaoru also regards Takeshi as his friend, feeling guilty for attacking him to the verge of death and due to this, finally losing his pride because he could not bear to fight Takeshi because he saved him and said that he wished to continue being friends with him before he was imprisoned by Vindice. After Demon was defeated, both reconciled and were seen playing baseball together again.