小维（广桥凉 配音）是一名标准的“电波少女”，表面上，她常常面无表情、一动不动，似乎无论这个世界发生了什么都跟她没有任何关系，但在内心里，有些孤独的小维还是希望能够得到他人的关心和友谊。
一次偶然中，一位名叫银仙（小野大辅 配音）的狐仙来到了小维的身边，由于担心小维的生活和健康状态，善良的银仙主动留在了小维身边，陪伴并照顾着她。之后，表面腹黑内心忠诚的狗神（樱井孝宏 配音）、放荡不羁的信乐（中田让治 配音）、傲娇的小玉（野上尤加奈 配音）接二连三的出现在了小维的面前，有了这些古怪但善良的朋友们陪伴，小维的生活中会发生怎样有趣的故事呢？

Takashi Natsume, the timid youkai expert and master of the Book of Friends, continues his journey towards self-understanding and acceptance with the help of friends both new and old.

Natsume, while briefly separated from Nyanko-sensei, is ambushed and kidnapped by a strange group of masked, monkey-like youkai, who have spirited him away to their forest as they desperately search for the Book of Friends. Realizing that his "servant" has been taken out from right under his nose, Nyanko-sensei enlists the help of Natsume's youkai friends and mounts a rescue operation. However, the forest of the monkey spirits holds many dangerous enemies, including the Matoba Clan, Natsume's old nemesis.

Stretching from the formidable hideout of the Matoba to Natsume's own childhood home, Natsume Yuujinchou Shi is a sweeping but familiar return to a world of danger and friendship, where Natsume will finally confront the demons of his own past.