One day, high-school boy Yamada bumps into the beautiful girl Shiraishi on the stairs (literally), and their lips touch as they fall. When they regain their wits, they realize that they have swapped bodies. As time progresses, the two realize that this is not the only mysterious happening in the school.

Grigio Academy Boarding School. Students who attend this school in two countries and reside in their own dormitories. Inazuka and Persia are rival dormitory leaders, but in secret they love each other. Now, they have to keep their relationship a secret from their dorm mates, or ruined things will happen to them.

Daichi Kakeru is a high school student who has never had a girlfriend. Little did he know that everything was about to change when he bought a melon soda on his way home from school as the can came to life in the form of a girl, whom he calls "Melon".

Chef Rashid invests all his money to open his own restaurant, but the project fails, and in a desperate attempt to save it, he reluctantly enters into a partnership with somebody, unaware that he may destroy all his dreams.

Itsuki Hashima is a light novelist obsessed with little sisters, strictly focusing on them when he writes his stories. Despite his personality, he's surrounded by a tight circle of friends, including a beautiful genius writer who loves him, a big-sisterly college classmate, a fellow male writer, a sadistic tax accountant, his editor, and Chihiro, his perfect younger step-brother who takes care of the housework and cooking. As the story progresses, the underlying conflicts of dreams and goals surface, as each character attempts to achieve their dreams, in their own way.

The central motif of the four-part love story Brush Me Tender, Brush Me Sweet is the complicated relationship between two surprising heroes who cannot be together, but neither can they be without each other, and are learning to live in a world affected by the coronavirus. They are Kartí and Pucinka, toothbrushes.