Self-professed "home security guard" Mahiro Oyama has not left his home in years, secluding himself in his room playing erotic visual novels. This depraved lifestyle causes his prodigious sister, Mihari, to worry about his well-being. In hopes of solving this problem, she devises a plan to rehabilitate him back to normalcy.

The first part of Mihari's plan is to concoct a medicine that changes her brother's biological constitution into a bona fide female, much to Mahiro's vehement dismay. Stuck in this predicament, Mahiro has no choice but to live out his life as a cute girl until the effect wears off—if it ever does.

Oniichan wa Oshimai! was released on Blu-ray in two boxes from April 19, 2023, to June 21, 2023.