The objective of this study is to evaluate the effectiveness and safety of Tripterygium glycosides combined with glucocorticoids for the treatment of refractory nephrotic syndrome (NS). Computer search of Chinese and English databases, including CNKI, VIP, Wan Fang Database, PubMed, Cochrane Library, Embase, and Sinomed, for randomized controlled trials (RCTs) of Tripterygium glycosides combined with glucocorticoids for refractory NS (RNS) was conducted. Meta-analysis was performed using RevMan5.3. Thirteen RCTs comprising 994 patients were included in the study. Tripterygium glycosides combined with glucocorticoids had a statistical significance on the effective rate (odds ratio [OR] =4.69, 95% confidence interval [CI] 3.29, 6.67, P < 0.00001), 24-h urine protein ( Weighted mean difference (MD) = -0.57, 95% CI [-0.62, -0.51], P < 0.00001), serum albumin (MD = 4.77,95% CI [4.30, 5.24], P < 0.00001), total serum protein (MD = 9.45, 95% CI [8.73, 10.17], P < 0.00001), urea nitrogen (MD = -0.53, 95% CI [-0.90, -0.17], P = 0.005), and serum creatinine (MD = -8.45, 95% CI [-15.32, -1.57], P = 0.02). There was no statistical significance on adverse reactions (OR = 0.68, 95% CI [0.41, 1.12], P = 0.13). Tripterygium glycosides combined with glucocorticoids could improve clinical effective rate, reduce 24-h urine protein, improve serum albumin and total serum protein, and reduce urea nitrogen and serum creatinine levels in patients with RNS. However, the quality of the included literature is poor, and conclusion still needs further verification using larger samples and high-quality randomized, double-blind controlled trials.