Osteoarthritis (OA), a prevalent joint disease affecting many people globally, presents significant challenge in current treatments, which often only manage symptoms without halting disease progression. This review illuminates novel approaches in OA therapy, focusing mainly on intra-articular injection of nanomaterials. The innovative materials, designed to either mimic or augment natural joint lubrication, show promise in restoring joint biomechanics and alleviating pain. The review delves into an array of biomimetic lubricants, including polymer brush, nanocomposite hydrogel, and nanoparticles, underscoring their roles in anti-inflammation, targeting, cartilage repair, and drug delivery. Furthermore, the potential of mesenchymal stem cells to differentiate into chondrocytes, coupled with the delivery of these cells and their exosomes via nanomaterials, has promoted cell therapy avenues for OA. The review also highlights the function of non-coding RNAs such as miRNA, siRNA, circRNA, lncRNA, and antisense oligonucleotides in impeding OA progression, with nanomaterials facilitating their delivery, thus facilitating advanced therapeutic possibilities including immune evasion and bone cell proliferation. Overall, this review encapsulates the evolution of nanomaterials in OA treatment from material to cell, and ultimately to gene therapy, forecasting a future where nanomaterials evolve toward integrated, personalized diagnostics and therapeutics for OA.