Osteoarthritis (OA) is a prevalent global health concern, posing a significant and increasing public health challenge worldwide. Recently, nanotechnology-boosted biomaterials have emerged as a highly promising strategy for OA therapy due to their exceptional physicochemical properties and capacity to regulate pathological processes. However, there is an urgent need for a deeper understanding of the potential therapeutic applications of these biomaterials in the clinical management of diseases, particularly in the treatment of OA. In this comprehensive review, we present an extensive discussion of the current status and future prospects concerning nanotechnology-boosted biomaterials for OA therapy. Initially, we discuss the pathophysiology of OA and the constraints associated with existing treatment modalities. Subsequently, various types of nanomaterials utilized for OA therapy, including nanoparticles, nanofibers, and nanocomposites, are thoroughly discussed and summarized, elucidating their respective advantages and challenges. Furthermore, we analyze recent preclinical and clinical studies that highlight the potential of nanotechnology-boosted biomaterials in OA therapy. Additionally, future research directions in this evolving field are highlighted. By establishing a link between the structural properties of nanotechnology-boosted biomaterials and their therapeutic functions in OA treatment, we aim to foster advances in designing sophisticated nanomaterials for OA, ultimately resulting in improved therapeutic efficacy of OA therapy through translation into clinical setting in the near future.