Ryohei is highly protective of his little sister who is often his prime motivation during his mafia fights. He was also determined to keep this side of his life a secret from Kyoko (usually by pretending the fights are sumo matches). Likewise Kyoko is also highly worried for her brother's safety and becomes frustrated whenever he fights. This was brought about due to the incident when they were children. Despite this she accepts his need to fight and supports him in his boxing.
Ryohei became impressed with Tsuna's strength in Dying Will Mode and as such continuously tries to recruit him to his Boxing Club. Tsuna who is often scared of Ryohei's enthusiasm nonetheless treats him like a brother (calling him "Big Brother" like Kyoko). As a result of his feelings for Kyoko, Tsuna is often worried that Ryohei will get hurt in fights and tries to talk him out of them. After Tsuna revealed the truth about the Mafia to Kyoko, Ryohei struck him in rage. However, Ryohei understood Tsuna's feelings and continues to respect him. After they came back from the alternate future, Kyoko told Tsuna that her brother blushes and gets embarrassed whenever Tsuna's name is mentioned.
Colonnello became Ryohei's tutor during the Varia arc. Colonnello soon saw Ryohei's potential and claimed he would become stronger than the other Guardians. They both share extreme attitudes which helped strengthen their bond and after training with Colonnello, Ryohei has also become more reserved (though still maintains a level of enthusiasm). In the Future, Ryohei continued to look up to Colonnello and was greatly saddened by his death, though he remained mostly calm about it.
Ryohei respects Hibari's power and wants him to involve himself with the rest of the family just like when he tried to drag Hibari into circle group at Vongola Ring Battle. Hibari's lone and quiet nature often clashes with Ryohei's persistent and loud one, which causes many arguments even if it is only for the smallest problem. However, Ryohei is one of a few people who are able to convince Hibari on something even though much less. Hibari also respects Ryohei enough not to interrupt his fights. Ryohei is probably the closest Guardian to Hibari and the only one to make so much efforts to befriend him despite the latter's constant refusal through force. In the Future, little has changed between them as Ryohei is still frustrated with Hibari's lack of cooperation and Hibari still ignores him but will always accept whenever Ryohei challenge him. Ryohei sometimes invites Hibari to a drink, which is always refused, much to his disappointment but this still doesn't stir his effort to befriend him, showing that he hasn't given up to make Hibari more sociable.
As sporting fanatics, Ryohei and Yamamoto have great respect for one another (Yamamoto even referring to Ryohei as Senpai). Like with Yamamoto, Gokudera has an unnecessary rivalry with Ryohei and as he is easy to frustrate this often leads to pointless arguments where they are eventually separated by Yamamoto. The future Ryohei also admitted to Gokudera that they share a hot temper and need to learn to keep their cool. They often call each other different names, Gokudera calls Ryohei Lawn-head or Turf-top, while Ryohei calls him Octopus-head. Despite this, Ryohei works well with both of them and all three support each other in their fights.
Ryohei developed a friendly but competitive rivalry with Kouyou soon after their first meeting. They actually have many similarities, such as their love of boxing and hatred of studying, though neither wants to be compared with the other. Both are short-tempered and easily get into a fight with their fist, which is the only thing they agree on with each other. Despite this, they respect each other when they broke the test plate, but refused to show it. Ryohei was greatly shocked when Kouyou revealed that his hatred for the Vongola came before his love of boxing but agreed to fight him nonetheless. Only after proving that they were of equal strength in battle, did they seem to finally accept each other. After the misunderstanding between the two families has been solved, both of them reconciled and much on friendly terms than before.