Objective This study systematically evaluated the efficacy and mechanism of action of Zhenwu Tang in treating diabetic kidney disease (DKD) using animal models. Methods Chinese and English databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Database, Chinese Biomedical Literature Service System, and VIP Information ) were searched from inception until June 2025. Experimental studies investigating Zhenwu Tang intervention in DKD animal models were included. The systematic review centre for laboratory animal experimentation tool was used to assess the quality, the GRADE-CERQual framework was applied to evaluate the certainty of evidence, and RevMan 5. 4 was used for statistical analysis. Results Thirteen studies were included, involving db / db mice and SD rat models. The primary modeling Methods induded streptozotocin ( STZ) injection or STZ combined with a high sugar and fat diet. Spleen-kidney yang deficiency syndrome was induced using a decoction of raw Rheum palmatum combined with hydrocortisone. Compared with model groups, Zhenwu Tang intervention significantly reduced key indicators, including serum creatinine, blood urea nitrogen, fasting plasma glucose, and 24-hour urinary protein excretion in DKD animals, though some studies did not observe a significant improvement in fasting plasma glucose with Zhenwu Tang intervention; it also ameliorated glomerulosclerosis, tubular injury, and renal fibrosis. The renal protective effects of Zhenwu Tang involve a multi-target network centered on crosstalk between suppressed nuclear factor-κB-mediated inflammation and activation of Nrf2-driven anti-oxidation,interconnected through reactive oxygen species modulation, leading to downstream effects such as key podocyte protection (upregulation of the key podocyte protein nephrin) and anti-fibrosis. The certainty of evidence was graded as “High” for biochemical parameters, urinary protein, and histopathological findings; “Moderate” for inflammation and oxidative stress markers; and “Low” for podocyte protein expression. Conclusions Zhenwu Tang exerts a renal protective effect in DKD animal models through a multi-target network centered on “ anti-inflammatory-antioxidant”crosstalk, which is dose- and time-dependent. Future more rigorous and high-quality basic studies are needed to verify these findings and further explore the optimal dose window and mechanism of action.