AIM: To observe the clinical efficacy of multi-glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ2 test were applied using own before-and-after control. RESULTS: After 6 months of treatment, the patient's albumin was (40.72±4.87) g/L, which was statistically different (P<0.05) compared with (35.86±7.90) g/L before treatment. The urinary albumin excretion rate (UACR) was (2 145±253) mg/g before treatment and (1 263±238) mg/g after treatment, with statistical differences before and after treatment (P<0.05); the total number of patients with severe urinary semiquantitative urine protein (3+, 4+) decreased compared with before, with statistically significant differences before and after treatment (P<0.05). Fasting Blood-Glucose (FPG) and Glycosylated Hemoglobin (HbA1c) were (8.42±3.31) mmol/L and (7.41±1.48)%, respectively, in patients after 6 months of treatment, which decreased compared with baseline FPG (7.20±1.95) mmol/L and HbA1c (6.63±1.00)% (P<0.05); During the treatment, the number of patients with glomerular filtration rate (eGFR) ≥3a stage blood creatinine (Scr) double increased was 1 (3.80%), the number of UACR double increased was 2 (7.70%), and the number of eGFR ≤3b stage was 0 and 1 (4.00%), respectively, and the difference between the two groups was not statistically significant (P>0.05); 3 cases (5.90%) had abnormal liver function and 1 case (2.00%) had leukopenia, which improved after treatment with liver protection and leukocyte-raising drugs. The difference of blood sugar, blood lipid and blood pressure before and after treatment did not show statistically significant (P>0.05). CONCLUSION: The use of GTW treatment in DKD patients can significantly reduce urinary protein, increase albumin and improve renal function, which is worthy of clinical promotion.