In the beginning of the series, Isshin is portrayed as a silly, fight-loving father who takes a keen interest in what his children are doing, but does it either offensively or with an all-too-happy tone, which elicits comical reactions from his kids, usually in the form of a kick. Isshin also seems to enjoy making fun of Ichigo and has a tendency to talk to the large memorial poster of his late wife Masaki, which he has pinned up in their kitchen, whenever he feels particularly emotional. Isshin is a big fan of Don Kanonji's TV show.

Isshin also shares a relationship with Ryuuken Ishida not unlike that of their sons. When Ryuuken discovers his son is missing, Isshin pays him a visit and the two chat about their respective styles of parenting. It is then revealed that Ryuuken was aware of Isshin's status, and he comments on Isshin's powers. The two have some prior history together, and that they have been acquaintances for quite some time. It can also be noted they both are doctors, Isshin runs a clinic while Ryuuken runs a hospital. There have been hints that the two cooperate on a professional level, with Isshin handling minor cases, and occasionally requesting aid from Ryuuken.

(Source: Bleach Wikia, Bleach Official Animation Book VIBEs)