"Nanaka 6/17" centers on Nanaka Kirisato, a 17-year-old high school student who, after a fall, regresses mentally to the age of six while retaining her adult body. This sudden change disrupts her life and relationships, particularly with her childhood friend Nenji Nagihara, who has grown distant due to Nanaka's previously cold and studious demeanor. Nenji, now a delinquent, is thrust into the role of caretaker as Nanaka's childlike innocence and curiosity resurface, forcing him to confront his own feelings and responsibilities.

The narrative explores the challenges of navigating adulthood while grappling with a child's mindset. Nanaka's regression brings humor and heartwarming moments as she interacts with the world through the lens of a six-year-old, often misunderstanding social norms and adult situations. Her condition also impacts her academic life, as she struggles to reconcile her advanced knowledge with her newfound emotional immaturity. Meanwhile, Nenji's efforts to protect and guide Nanaka reveal his underlying loyalty and affection, rekindling their bond.

Supporting characters include Arashiko Tachibana, Nanaka's best friend, who provides emotional support and helps bridge the gap between Nanaka's past and present self. The story also delves into the dynamics of Nanaka's family, particularly her father, who struggles to adapt to her sudden change. Themes of identity, memory, and the complexities of human relationships are woven throughout the narrative, as Nanaka's journey oscillates between comedic and poignant moments.

The series balances lighthearted humor with deeper emotional undertones, examining how trauma and regression can reshape relationships and personal growth. Through its exploration of Nanaka's dual existence as both a child and an adult, "Nanaka 6/17" offers a unique perspective on the challenges of maturity and the enduring power of friendship.