Osteoarthritis (OA) of the knee is the most prevalent degenerative joint condition that places a substantial financial and medical burden on society. However, due to drawbacks such as inefficiency, adverse effects, and brief duration of action, the clinical efficacy of the current major therapies for knee OA is largely restricted. Therefore, novel medication development is highly required to address these issues. Numerous studies in recent years have established that nanomaterials can be a potential and highly effective way to overcome these challenges. In this review, the anatomical distinctions between healthy and OA knee joints, as well as novel advances in the field of nanomaterials for the treatment of knee OA are summarized. The limits of the present therapeutic strategies for treating knee OA are also highlighted, as well as the potential prospects of nanomaterials in the future. Given its excellent biocompatibility, high specific surface area, facile surface modification features, and unique physicochemical properties, the novel nanomaterials have paved a new way for the treatment of OA. Simultaneously, the pathophysiological and structural characteristics of OA also offer design criteria for the preparation of nano-theranostic agents for OA. This research provides some feasible strategies for the development of innovative treatment approaches for OA. image