"Dropkick on My Devil!" centers on the chaotic and comedic relationship between Yurine Hanazono, a college student, and Jashin-chan, a snake demon from the underworld. The story begins when Yurine summons Jashin-chan to the human world through a ritual, only to find herself stuck with the mischievous and lazy demon. Unable to return to her realm, Jashin-chan becomes Yurine's reluctant roommate, leading to a series of absurd and often violent interactions.

Jashin-chan frequently attempts to kill Yurine in hopes of breaking the summoning contract, but her efforts are consistently thwarted, often resulting in her own suffering. Despite her antagonistic nature, Jashin-chan forms an odd camaraderie with other supernatural beings, including Pekola, an angel sent to monitor her, and Medusa, a gorgon who becomes Jashin-chan's rival. The series explores their daily lives, blending slapstick humor, dark comedy, and occasional moments of unexpected warmth.

The narrative is episodic, with each episode focusing on the characters' misadventures, ranging from mundane tasks like grocery shopping to more fantastical scenarios involving magical artifacts or underworld politics. Yurine's pragmatic and often cruel demeanor contrasts sharply with Jashin-chan's brash and impulsive personality, creating a dynamic that drives much of the humor. Supporting characters, such as Minos, a minotaur who works at a convenience store, and Poporon, a slime-like creature, add further layers to the chaotic world.

Themes of friendship, rivalry, and the absurdity of coexistence between humans and demons are explored through the characters' interactions. While the tone is predominantly comedic, the series occasionally delves into the characters' backstories, providing glimpses into their motivations and vulnerabilities. The blend of supernatural elements, over-the-top violence, and quirky character dynamics makes "Dropkick on My Devil!" a distinctive entry in the comedy genre.