Using her wit and vast knowledge of medicines and poisons alike, Maomao played a pivotal role in solving a series of mysteries and conspiracies that plagued the imperial court. Having recently come to terms with the secrets of her parents, she returns to fulfill her normal duties on behalf of the emperor's highest-ranking consorts. Maomao also works alongside the eunuch Jinshi to better the consorts' many ladies-in-waiting, including helping them learn to read.

However, with the arrival of a merchant caravan comes a new wave of intrigue. A pattern of strange coincidences involving the visitors and their wares unsettles Maomao, driving her to investigate the puzzling circumstances behind the convoy. As dangers from both outside and within threaten the balance between the imperial concubines, Maomao continues to utilize her cunning and medical expertise to keep the women safe from harm.

Kusuriya no Hitorigoto 2nd Season aired on Nippon TV's Friday Anime Night block. It was released on Blu-ray in four volumes by Toho from April 16, 2025, to October 15, 2025. The series adapts the third and fourth volume of the light novel.