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The effect of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) therapy on knee osteoarthritis (KOA) has been contradictory in previous meta-analyses. This umbrella review on published meta-analyses aimed to investigate the effect of MSCs and PRP on KOA. We systematically searched Scopus, PubMed, and Cochrane databases to include related meta-analyses. The outcome included studies reporting visual analog scale scores, the Western Ontario and McMaster Universities Osteoarthritis Index, Whole-Organ Magnetic Resonance Imaging Scores, International Knee Documentation Committee scores, and the Knee injury and Osteoarthritis Outcome Score. A total of 28 meta-analyses with 32 763 participants. MSCs and PRP therapies were significantly associated with an improvement in KOA scores. This umbrella meta-analysis supports the beneficial health effects of MSCs and PRP in KOA.