To systematically evaluate the efficacy and safety of tripterygium glycosides combined with leflunomide in the treatment of rheumatoid arthritis.Methods:The Cochrane Library，Web of Science，PubMed，CNKI，CBM，WanFang Data，and VIP were searched from database inception to August 14，2020，for the clinical trial data of tripterygium glycosides combined with leflunomide in the treatment of rheumatoid arthritis.Cochrane Handbook for Systematic Reviews of Interventions (5.1.0) was used for quality evaluation and RevMan 5.3 for data analysis.Results:Thirteen randomized controlled trials (RCTs) were included，with 1 004 patients with rheumatoid arthritis involved，including 503 in the observation group and 501 in the control group.As revealed by Meta-analysis results，the observation group was lower than the control group in morning stiffness time [SMD=-1.55，95%CI (-1.87 to -1.23)，SMD=-2.29，95%CI (-3.46 to -1.12)]，number of joint pain [SMD=-0.94，95%CI (-1.40 to -0.49)]，number of joint swelling [SMD=-0.78，95%CI (-1.52 to -0.04)]，erythrocyte sedimentation rate [SMD=-1.75，95%CI (-2.38 to -1.13)]，C-reactive protein [SMD=-2.23，95%CI (-2.96 to -1.51)]，rheumatoid factor [SMD=-2.97，95%CI (-4.22 to -1.72)]，immunoglobulin G [SMD=-0.58，95%CI (-1.10 to -0.06)]，interleukin-1 [SMD=-0.84，95%CI (-1.20 to -0.49)]，interleukin-6 [SMD=-4.08，95%CI (-4.86 to -3.30)]，tumor necrosis factor-α [SMD=-3.24，95%CI (-3.92 to -2.56)，SMD=-0.94，95%CI (-1.30 to -0.57)]，and soluble intercellular adhesion molecule-1 [SMD=-0.53，95%CI (-0.96 to -0.10)].The total clinical effective rate of the observation group was better than that of the control group [OR=4.12，95%CI (2.74 to 6.18)].There was no significant difference between the observation group and the control group in rest pain，immunoglobulin A，immunoglobulin M，interleukin-10，and the incidence of adverse events.Conclusion:Tripterygium glycosides combined with leflunomide in the treatment of rheumatoid arthritis can increase the total clinical effective rate of patients and improve the signs and symptoms of rheumatoid arthritis patients with good safety，which is worthy of clinical promotion.However，due to the limitations of the quality of the included RCTs and the influence of clinical heterogeneity，the results still need to be verified by clinical practice.