Tripterygium wilfordii Hook F (TwHF) is a promising Chinese traditional medicine used to significantly reduce proteinuria and improve renal function. However, its efficacy and safety in treatment of chronic kidney disease need to be further explored in order to promote its application in clinics. This review compared the efficacy and safety of TwHF with the placebo, conventional Western medicine and other immunosuppressive medicine in a range of kidney disorders. One hundred three randomized controlled trials were included. TwHF therapy decreased 24-hr proteinuria by 0.59g/day (95% confidence interval [CI; -0.68, -0.50]), serum creatinine level by 1.93mol/L (95% CI [-3.69, -0.17]), and blood urea nitrogen level by 0.24mmol/L (95% CI [-0.41, -0.07]); increased the total effective rate by 27% (95% CI [1.24, 1.30]); and decreased the incidence of adverse reactions by 19% (95% CI [0.68, 0.96]) overall. Meta regression results showed that the duration of therapy and mean age of participants were the major sources of high heterogeneity. Sensitivity analysis demonstrated that our statistic results were relatively stable and credible. The present findings suggested that TwHF possibly has nephroprotective effects by decreasing proteinuria, serum creatinine level, and blood urea nitrogen level and no more adverse reactions compared with control group in most kidney disorders. However, these findings still need to be further confirmed by high-quality trials.