"Younger Sister Juice" centers around the life of Haruto, a high school student who finds himself in an unusual predicament after his parents leave him in charge of his younger sister, Yui, for an extended period. Yui, a middle schooler with a mischievous streak, often tests Haruto's patience with her antics, but their relationship takes a peculiar turn when she begins experimenting with homemade juice recipes. These concoctions, made from bizarre ingredients, have unexpected effects on those who consume them, leading to a series of comedic and surreal situations.

The narrative unfolds as Haruto navigates the challenges of balancing his school life, part-time job, and the chaos Yui brings into their home. Each episode typically revolves around a new juice recipe, with Yui's creations causing transformations, heightened emotions, or strange behaviors in Haruto and others around them. The series explores themes of sibling dynamics, responsibility, and the absurdity of everyday life through its episodic structure.

Key characters include Haruto, the pragmatic and often exasperated older brother; Yui, the curious and unpredictable younger sister; and a supporting cast of classmates and neighbors who frequently become unwitting participants in Yui's experiments. The interactions between Haruto and Yui form the core of the story, blending humor with moments of genuine sibling bonding. The series maintains a lighthearted tone, using the fantastical elements of the juice recipes to amplify the comedic and heartfelt aspects of the characters' relationships.