Abstract: Objective To investigate the efficacy and oxidative stress mechanism of Jiangtang Yishen Pill combined with dapagliflozin in the treatment of early-to-middle stage diabetes chronic nephropathy. Methods A total of 196 patients with early-to-middle stage diabetes chronic nephropathy admitted to the Second Affiliated Hospital of Hunan University of Chinese Medicine from March 2023 to January 2025 were enrolled. They were randomly divided into an intervention group(receiving Jiangtang Yishen Pill combined with dapagliflozin) and a control group(receiving dapagliflozin alone), with 98 patients in each group. Both groups were treated for 12 weeks. The clinical efficacy after 12 weeks of treatment, blood glucose, renal function, and oxidative stress indicators after 4 and 12 weeks of treatment, as well as adverse reactions within 12 weeks of treatment, were compared between the two groups. Results The total effective rate in the intervention group was significantly higher than that in the control group(P<0.05). After 4 and 12 weeks of treatment, the levels of blood glucose indicators(fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin), renal function indicators(blood urea nitrogen, serum creatinine, and urinary albumin excretion rate), as well as malondialdehyde in the intervention group were significantly lower than those in the control group(P<0.05), while the levels of superoxide dismutase and total antioxidant capacity were significantly higher than those in the control group(P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups(P>0.05). Conclusion The combination of Jiangtang Yishen Pill and dapagliflozin improves blood glucose control and renal function in patients with early-to-middle stage diabetes chronic nephropathy. Furthermore, it alleviates oxidative stress and enhances the overall clinical efficacy.