Objective To analyze the correlation between serum uric acid (UA) and cystatin C (CysC) expression and diabetic nephropathy (DN) in diabetic patients. Methods The clinical data of 87 patients with diabetes treated in our hospital from April 2022 to June 2024 were retrospectively collected. According to the diagnosis results of diabetic nephropathy, the patients were divided into DN developing group and non-developing group. Baseline data were collected and compared between the two groups. Serum UA and CysC levels were detected and compared between the two groups. Logistic regression model and point two-column correlation test were used to analyze the correlation between serum UA and CysC expression and DN in diabetic patients. Results Among 87 diabetic patients, 29 cases developed DN and were included in the development group. There were 58 cases without DN, which were included in the group without DN. The levels of serum UA and CysC in the occurrence group were significantly higher than those in the non-occurrence group (P < 0.05). Logistic regression model analysis showed that the complications of DN in diabetic patients may be related to the overexpression of serum UA and CysC (P < 0.05). Point two-column correlation analysis showed that the expression of serum UA and CysC was positively correlated with DN in diabetic patients (P < 0.05). Conclusion There is a positive correlation between DN and serum UA and CysC overexpression in diabetic patients.