BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability, with current treatment options often falling short of providing satisfactory outcomes. Autologous-cultured adipose-derived mesenchymal stem cells (ADMSCs) and stromal vascular fractions (SVFs) have emerged as potential regenerative therapies. METHODS: A comprehensive search was conducted among multiple databases for studies up to June 2023. The risk of bias was assessed in randomized and non-randomized studies, adhering to PRISMA guidelines. The study has been registered with PROSPERO (CRD 42023433160). RESULTS: Our analysis encompassed 31 studies involving 1,406 patients, of which, 19 studies with 958 patients were included in a meta-analysis, examining both SVF and autologous-cultured ADMSC methods. Significant pain reduction was observed with autologous-cultured ADMSCs starting at 3 months (MD = -2.43, 95% CI, -3.99, -0.86), whereas significant pain mitigation in response to SVF therapy was found to start at 12 months (MD = -2.13, 95% CI, -3.06, -1.21). Both autologous-cultured ADMSCs and SVF provided significant improvement in knee function starting at 12 months (MD = -9.19, 95% CI, -12.48, -5.90 vs. MD = -9.09, 95% CI, -12.67, -5.51, respectively). We found no evidence of severe adverse events linked directly to ADMSC therapy. CONCLUSION: Autologous-cultured ADMSCs offer a promising alternative for more rapid pain relief in knee OA, with both ADMSCs and SVF demonstrating substantial long-term benefits in joint function and cartilage regeneration, in the absence of any severe ADMSC-related adverse events.