Yayoi Sanzenin is the popular school nurse at Koyomi Academy, attracting numerous male students who feign illness for her attention. She dons a long white nurse coat and tight skirt at school but changes into her family's traditional Japanese priest attire at home. Born into the Tonami-style Sanzenin family, she is the 13th-generation miko. Her parents serve as kannushi at their temple, where Yayoi assists during her off-hours. This heritage grants her heightened spiritual sensitivity and training, which intensify after moving in with Chitose Hitotose. This amplified spiritual awareness sharpens her typically calm demeanor into vigilant responses whenever she perceives threats to Chitose.

As one of the five teachers residing with Chitose in a maternal capacity, Yayoi blends nurturing care with disciplined enforcement. Proficient in kendo, she wields a katana, pressing it against his neck when necessary to compel compliance. This juxtaposition of spiritual serenity and readiness for physical intervention defines her approach to guiding him. Within the household, she shares domestic duties with the other teachers, collectively striving to improve Chitose's behavior and academics. Her protective nature remains consistent throughout the series. In the concluding OVA, *The Final*, she joins efforts with Chitose and the other teachers to preserve the academy's old school building, culminating in all five teachers transitioning into romantic partners for Chitose within a communal marriage.