To evaluate the effects and safety of Tripterygium wilfordii polyglycoside (TWP) in the treatment of immunoglobulin A (IgA) nephropathy. A computer-assisted study search of Chinese Biomedical Database (CBM), Chinese Journal Full-text Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (VIP), PubMed, Medline, EMBASE and Cochrane Library was performed, with the time range of retrieval set between the establishment of the database to December 31, 2019. Articles of randomized controlled trials on the treatment of IgA nephropathy by Tripterygium wilfordii polyglycoside were collected, and then screened according to the inclusion and exclusion criteria. Next, the quality of the papers was assessed, effective data were extracted, and a meta-analysis of the included studies was conducted using the Review Manager 5.3 software provided by the Cochrane Collaboration. Thirty randomized controlled trials (RCT) were included ultimately, and the meta-analysis showed that 1) Single (Sgl) TWP group was superior to angiotensin-converting enzyme inhibitor/angiotension receptor blocker (ACEI/ARB) group in terms of complete remission [odds ratio (OR) = 4.74, p-value < 0.00001], total remission (OR = 3.90, p-value < 0.0001), 24-hour proteinuria [mean difference (MD) = 1.18, p-value < 0.00001], and serum albumin (MD = - 8.23, p-value < 0.00001), and no significant difference in serum creatinine (MD = 2.09, p-value = 0.08) was found between Sgl TWP and control groups; TWP + ACEI/ARB group was superior in complete remission (OR = 2.57, p-value < 0.00001), total remission (OR = 4.36, p-value < 0.00001), serum albumin [standardized mean difference (SMD) = -0.68, p-value = 0.0005], 24-hour proteinuria (SMD = 1.24, p-value < 0.00001) and serum creatinine (SMD = 0.48, p-value = 0.006); 2) TWP group was superior to glucocorticoid group in complete remission (OR = 1.93, p-value < 0.0010), total remission (OR = 3.71, p-value < 0.00001), serum albumin (MD = -3.50, p-value = 0.002), 24-hour proteinuria (SMD = 0.93, p-value < 0.0001) and serum creatinine (SMD = 0.88, p-value = 0.006); 3) TWP group was better than mycophenolate mofetil (MMF) group in complete remission (OR = 2.05, p = 0.005), total remission (OR = 3.30, p-value = 0.002), 24-hour proteinuria (MD = 2.61, p-value < 0.0001), and serum albumin (MD = -6.43, p-value < 0.00001), but the differences in serum creatinine (MD = 1.28, p-value = 0.89) between TWP and control groups were not significant. Besides, TWP + ACEI/ARB group had a higher adverse reaction rate than the control group (OR = 2.21, p-value = 0.04), but there was no significant difference in the adverse reaction rate between other control and experimental groups (p-value > 0.05). The present evidence shows that Tripterygium wilfordii polyglycoside can effectively improve the remission rate, reduce proteinuria, and protect kidney function of IgA nephropathy patients, and also has good safety. However, limited by the quality of the included studies, the effects and safety of Tripterygium wilfordii polyglycoside in the treatment of IgA nephropathy need to be verified by more high-quality, large-scale, multi-center RCTs.