BACKGROUND: Intra-articular administration of mesenchymal stem cells (MSCs) presents a novel methodology for managing osteoarthritis, but there is still no definite evidence of its efficacy. AIM: To assess the comparative effectiveness of MSCs and platelet-rich plasma (PRP) for managing osteoarthritis by reviewing the literature and using meta-analysis. METHODS: Randomized controlled trials and cohort studies comparing MSCs and PRP for managing osteoarthritis were included. We searched 'osteoarthritis', 'mesenchymal stem cell', 'platelet-rich plasma', and other words in Pubmed, Embase, and Cochrane Library database. The search period encompassed the entire duration of the databases, starting from its inception until April 2024. Two researchers conducted the literature search, extracting data, and evaluating quality as distinct processes. Meta-analysis was carried out using the software RevMan5.3, and the calculation of weighted mean difference (WMD) and 95% confidence interval (CI) were performed using either a fixed-effect model or a random-effects model. RESULTS: Eleven studies were included, comprising 8 randomized controlled trials and 3 cohort studies. A total of 693 individuals participated in the study, of which 394 received intra-articular injections of MSCs (group A) and 299 received intra-articular injections of PRP (group B). The two groups were comparable in the five dimensions of knee injury and osteoarthritis outcome score (KOOS) [pain (WMD: 0.38, 95% CI: -3.62 to 4.38, > 0.05), symptoms (WMD: -1.48, 95% CI: -5.90 to 2.94, > 0.05), activities of daily living (ADL, WMD: -2.36, 95% CI: -6.87 to 2.14, > 0.05), function in sport and recreation (Sport/Rec, WMD: -3.84, 95% CI: -10.60 to 2.92, > 0.05), knee-related quality of life (QOL, WMD: 0.09, 95% CI: -5.48 to 5.67, > 0.05)] and Western Ontario and McMaster Universities osteoarthritis index (WOMAC, WMD: 0.47, 95% CI: -3.76 to 4.70, > 0.05). Compared with group A, the International Knee Documentation Committee Subjective Knee Form (IKDC, WMD: 4.19, 95% CI: 2.57 to 5.82, < 0.001) score of group B was higher. CONCLUSION: The short-term effectiveness of intra-articular administration of PRP for managing osteoarthritis is slightly better than that of MSCs. However, because of the limited quantity of incorporated research studies and the potential for bias, requisite in the future are studies of substantial size and superior quality.