Oniichan wa Oshimai! centers on Mahiro Oyama, a self-proclaimed "home security guard" who has spent years shut away, drifting deeper into isolation and filling his days with erotic visual novels. His younger sister, Mihari, becomes increasingly alarmed by the life he has built for himself and decides to intervene in the most extreme way possible: she gives him a potion that turns Mahiro into a girl. The transformation leaves him shocked and embarrassed, but it also forces him to face ordinary life from a completely new perspective.
From there, the comedy follows Mahiro as he tries to adapt to his changed body and to the strange new reality Mihari has created around him. What was meant as an intervention becomes a bizarre daily routine, with the siblings caught between concern, frustration, and an unusually complicated family bond. As Mahiro stumbles through everyday situations and Mihari tries to manage the consequences of her experiment, Oniichan wa Oshimai! builds its humor around isolation, dependence, and the chaos that comes from trying to drag someone back into the world by turning his life upside down.