"Sister Princess" centers around Wataru Minakami, a young man who unexpectedly finds himself at Promised Island, a mysterious and isolated place, after failing his high school entrance exams. Upon arrival, Wataru discovers he has twelve sisters, each with distinct personalities and backgrounds, who all adore him and refer to him as their "big brother." The sisters—Aria, Karen, Mamoru, Marie, Haruka, Kaho, Yotsuba, Rinrin, Chikage, Shirayuki, Sakuya, and Marine—are deeply affectionate toward Wataru, often competing for his attention and affection in lighthearted, comedic ways.

The narrative unfolds in a slice-of-life format, focusing on the daily interactions and bonding between Wataru and his sisters. Each sister has her own quirks and interests, ranging from cooking and music to science and martial arts, which adds variety to the episodic structure of the story. Wataru, initially overwhelmed by the sudden responsibility of being a brother figure, gradually grows closer to each sister, learning about their individual dreams, fears, and aspirations. The series emphasizes themes of familial love, acceptance, and the importance of relationships, often blending heartwarming moments with light comedy.

While the premise revolves around the sisters' adoration for Wataru, the story avoids delving into overly dramatic or conflict-driven plots, instead maintaining a gentle, wholesome tone. The setting of Promised Island, with its idyllic landscapes and serene atmosphere, complements the story's focus on familial bonds and personal growth. The manga explores the dynamics of a non-traditional family, highlighting how Wataru and his sisters navigate their relationships and support one another in their daily lives. The series is characterized by its episodic nature, with each chapter or volume often focusing on a specific sister or a particular event, allowing for a deeper exploration of their personalities and connections with Wataru.