"Ani ni Tsukeru Kusuri wa Nai!" centers on the comedic and chaotic sibling relationship between Shi Miao, a high school girl with a sharp tongue and a fiery temper, and her older brother Shi Fen, a laid-back and carefree college student. Despite their constant bickering and Shi Miao's frequent physical outbursts toward her brother, the two share a deep, albeit unconventional, bond. The series explores their daily lives, filled with exaggerated yet relatable sibling antics, as they navigate school, friendships, and family dynamics.

Shi Miao is portrayed as fiercely protective of her brother, often intervening in his romantic pursuits or defending him from others, though her actions are typically laced with sarcasm and violence. Shi Fen, on the other hand, is easygoing and often oblivious to his sister's overbearing nature, which only fuels their comedic clashes. The narrative is episodic, with each episode presenting self-contained scenarios that highlight the siblings' contrasting personalities and their ability to inadvertently support each other despite their constant quarrels.

The supporting cast includes characters like Xiao Qian, Shi Fen's childhood friend and love interest, who often becomes a target of Shi Miao's jealousy and overprotectiveness. Other characters, such as classmates and acquaintances, add variety to the comedic situations, further emphasizing the siblings' dynamic. The humor is rooted in slapstick comedy, exaggerated reactions, and the absurdity of their interactions, making the series lighthearted and entertaining.

Themes of family, loyalty, and the complexities of sibling relationships are woven throughout the narrative, though the focus remains on humor and the exaggerated portrayal of everyday situations. The series balances its comedic tone with moments of genuine warmth, showcasing the underlying affection between Shi Miao and Shi Fen despite their constant clashes. The episodic structure ensures a steady pace, with each episode delivering a mix of laughter and light-hearted drama.