Objective: To analyze the clinical effect of using finerenone combined with irbesartan in the treatment of diabetic nephropathy. Methods: Eighty-five patients with diabetic nephropathy who received inpatient treatment in our hospital from July 2023 to June 2024 were selected and divided into the control group (42 cases) and the observation group (43 cases) according to the differences in drug treatment programs. The control group received oral treatment with finerenone tablets, and the observation group received treatment with finerenone combined with irbesartan. The differences in the blood glucose level, renal function indicators, serological level, and adverse reactions of the two groups were compared and analyzed. Results: After treatment, the levels of fasting blood glucose, 2-hour postprandial blood glucose, glycated hemoglobin, blood creatinine, urea nitrogen, blood uric acid, TGF-β1, SFRP-4, GSK-3β, and ICAM-1 in the observation group were significantly lower than those in the control group (P < 0.05). In the control group, there was one case each of vertigo, palpitation, rash, vomiting, and angioneurotic edema during treatment, with a total incidence rate of 11.90%; the observation group had one case each of vertigo and vomiting, with a total incidence rate of 4.65% (P > 0.05). Conclusion: In the clinical treatment of patients with diabetic nephropathy, finerenone combined with irbesartan therapy can significantly improve patients’ blood glucose level and serological levels, and alleviate patients’ renal function, showing positive clinical application value.