"PetoPeto-san" is a supernatural comedy anime centered around the peculiar relationship between a high school boy named Shingo and a ghost girl named Petoko. Shingo, an ordinary student, discovers that he has the ability to see spirits after a near-death experience. This newfound ability leads him to encounter Petoko, a mischievous and clumsy ghost who haunts his school. Unlike typical ghosts, Petoko is not malevolent but rather playful and often causes unintentional trouble due to her lack of control over her ghostly powers.

The narrative explores the daily interactions between Shingo and Petoko as they navigate the challenges of coexisting in the human world. Shingo, initially reluctant to be involved with spirits, gradually becomes accustomed to Petoko's presence and even develops a sense of responsibility toward her. Petoko, on the other hand, is portrayed as a carefree and somewhat naive spirit who enjoys her time with Shingo, often dragging him into humorous and chaotic situations. The series balances lighthearted comedy with moments of emotional depth, particularly as Petoko's backstory and the reasons for her lingering in the human world are revealed.

Supporting characters include Shingo's classmates and other spirits who occasionally appear, adding variety to the story. The interactions between the human and spirit worlds are a recurring theme, with the series often highlighting the contrast between the mundane lives of the living and the peculiar existence of ghosts. The episodic structure of the anime allows for a mix of standalone comedic scenarios and gradual development of the central relationship between Shingo and Petoko. While the tone remains predominantly comedic, the series occasionally touches on themes of loneliness, attachment, and the transient nature of life, providing a nuanced backdrop to the otherwise whimsical narrative.