The article reviews the potential of mesenchymal stem cell-derived exosomes (MSC-Exos) as a promising cell-free therapy for knee osteoarthritis (OA). OA is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, osteophyte formation, and synovial inflammation. Current treatments focus on symptomatic relief, but do not slow disease progression. MSC-Exos, which are bioactive factor carriers, have shown promising results in preclinical studies for OA treatment. The review explores the mechanisms by which MSC-Exos mitigate OA, including promoting chondrocyte proliferation, inhibiting apoptosis, reducing inflammation, and maintaining extracellular matrix (ECM) balance. Various strategies for engineering MSC-Exos, such as cargo loading, surface modification, and combining with biomaterials, are discussed to enhance their therapeutic efficacy. Despite the potential of MSC-Exos, challenges remain, including the need for standardized preparation methods, large-scale production, and addressing immune responses. Clinical trials are underway to evaluate the safety and effectiveness of MSC-Exos therapy for OA, and the authors conclude that MSC-Exos show promise as a cell-free therapy for knee OA.The article reviews the potential of mesenchymal stem cell-derived exosomes (MSC-Exos) as a promising cell-free therapy for knee osteoarthritis (OA). OA is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, osteophyte formation, and synovial inflammation. Current treatments focus on symptomatic relief, but do not slow disease progression. MSC-Exos, which are bioactive factor carriers, have shown promising results in preclinical studies for OA treatment. The review explores the mechanisms by which MSC-Exos mitigate OA, including promoting chondrocyte proliferation, inhibiting apoptosis, reducing inflammation, and maintaining extracellular matrix (ECM) balance. Various strategies for engineering MSC-Exos, such as cargo loading, surface modification, and combining with biomaterials, are discussed to enhance their therapeutic efficacy. Despite the potential of MSC-Exos, challenges remain, including the need for standardized preparation methods, large-scale production, and addressing immune responses. Clinical trials are underway to evaluate the safety and effectiveness of MSC-Exos therapy for OA, and the authors conclude that MSC-Exos show promise as a cell-free therapy for knee OA.