Osteoarthritis (OA) is characterized mainly by articular cartilage loss, subchondral osteosclerosis, and chronic inflammation and involves multiple types of cellular dysfunction and tissue lesions. The rapid development of nanotechnology and materials science has contributed to the application of biomimetic nanomaterials in the biomedical field. By optimizing the composition, hardness, porosity, and drug loading of biomimetic nanomaterials, their unique physicochemical properties drive potential applications in bone repair. This article reviews the present understanding of the physiopathological mechanism and clinical treatment drawbacks of OA and summarizes various types of biomimetic nanomaterials for OA that target lesion sites, such as cartilage, subchondral bone, and synovium, through simulation of the physiological structure and microenvironment. Eventually, the challenges and prospects for the clinical translation of biomimetic nanomaterials are further discussed, with the goal of accessing an effective approach for OA treatment.