Objective: To investigate the efficacy of dapagliflozin combined with valsartan in the treatment of diabetic kidney disease (DKD).Methods: A total of 220 patients with DKD were divided into two groups according to different treatment options: a control group (n=107) and an observation group (n=106). The control group received valsartan monotherapy, while the observation group received dapagliflozin combined with valsartan. Both groups were treated for 12 weeks. Changes in urinary protein indicators [24-hour urinary albumin excretion (24h UAE), urinary albumin-to-creatinine ratio (ACR)], renal function [serum creatinine (Scr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR)], fibrosis markers [tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1 (TGF-β1)], and oxidative stress indicators [8-hydroxy-2'-deoxyguanosine (8-OHDG), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD)] were compared between the two groups. Therapeutic efficacy was also evaluated.Results: A total of 213 patients eventually completed the trial, with 107 in the control group (3 withdrew) and 106 in the observation group (4 dropped out). After treatment, the total effective rate was higher in the observation group than that in the control group (90.57% vs. 77.57%, P<0.05). In the observation group, the 24h UAE, ACR, Scr, and BUN were lower than those in the control group (P<0.05), and the eGFR level was higher than that in the control group (P<0.05). The serum levels of TIMP-1, TGF-β1, 8-OHDG, and 3-NT in the observation group were lower than those in the control group (P<0.05), while the SOD level was higher than that in the control group (P<0.05).Conclusion: Dapagliflozin combined with valsartan inhibits oxidative stress, ameliorates renal fibrosis, and provides superior renal protection, thereby enhancing therapeutic efficacy in DKD patients.