Kiken na Anesan follows the life of Hiroko Minagawa, a woman who has lived her entire life in the shadow of her younger brother, Yutaro. While Hiroko is known for being clumsy, unlucky, and academically challenged, Yutaro is a genius medical student who is cold, calculating, and often embarrassed by his sister's antics. After Hiroko moves to Tokyo to live with him, their contrasting personalities lead to constant friction and comedic misunderstandings. As the series progresses, the dynamic between the two shifts as they navigate the complexities of adulthood, career struggles, and romantic entanglements. Despite their bickering, the bond between the siblings is tested and strengthened, revealing that beneath Yutaro's icy exterior lies a deep concern for his sister, and beneath Hiroko's chaotic nature is a genuine, selfless heart that eventually influences those around her.