Objective. Osteoarthritis (OA) is the most common degenerative joint disease, causing joint pain, stiffness, and even disability. Guidelines recommend intra-articular injections as an alternative treatment to relieve OA symptoms for patients who demonstrate poor tolerability or compliance to oral administration of drugs. Mesenchymal stem cells (MSCs) are a potential treatment for of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety between hyaluronic acid (HA), corticosteroids (GCs), platelet-rich plasma (PRP), and MSCs. Design. Systematic review and Bayesian network meta-analysis. Data Sources. Relevant studies, published from January 2000 to January 2020, in the PubMed, Cochrane library, EMBASE, and CKNI databases. Methods. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement, improvement in joint stiffness, and risk of adverse effects (AEs) were assessed. Results. Twenty-five articles with 4642 patients were included. Overall, MSC therapy was the most effective treatment for pain relief (standardized mean difference compared with placebo=3.61, 95% CI [1.87 to 5.35]). Both MSC and PRP therapies improved every symptom of OA effectively and have an advantage over HA and GCs which are recommended by guidelines. MSCs, PRP, HA, and GCs are tolerated well for patients in long-term treatment of OA compared with placebo. Conclusions. The results show that MSCs relieve pain, stiffness, and dysfunction due to OA better than PRP, HA, and GCs and are not statistically correlated with greater safety concerns. More high-quality trials are needed to reconfirm the findings of this study, however, standardization of preparation of MSCs and PRP should be investigated in the future.