Objective To investigate the therapeutic value of Xuelian Yishen granules in elderly patients with stages Ⅲ-Ⅳ diabetic kidney disease (DKD) of spleen-kidney qi deficiency pattern, and explore the effects on the levels of serum inflammatory factors and urinary podocyte slit diaphragm protein (Nephrin) and membrane protein (Podocin). Methods A total of 115 elderly patients with stages Ⅲ-Ⅳ DKD and syndrome differentiation of spleen-kidney qi deficiency syndrome admitted to Urumqi hospital of traditional Chinese medicine from August 2022 to September 2024 were enrolled and randomly divided into a Xuelian group (losartan potassium tablets plus Xuelian Yishen granules, n=57) and control group (losartan potassium tablet, n=56). After 3 months of continuous treatment, glucose metabolism indicators, renal function indicators, serum inflammatory factors, and urinary Nephrin and Podocin levels were compared between groups. The effective rate of treatment and efficacy of traditional Chinese medicine (TCM) syndromes were also evaluated and compared. Data analysis was performed by using SPSS 26.0 statistics. Depending on data type, independent samples t-test, paired samples t-test or Chi-square test was applied for comparisons between groups. Results The effective rate of treatment and effective rate of TCM syndromes were significantly higher in the Xuelian group than the control group (94.74% vs 62.07%, 94.74% vs 60.34%, both P<0.05). After treatment, urinary albumin excretionrate, urine microalbumi, blood urea nitrogen, serum creatinine, interleukin-6, tumor necrosis factor-α, Nephrin and Podocin in both groups were all decreased compared with those before treatment, and the above indicators in Xuelian group after treatment were lower than those in control group (all P<0.05). Conclusion Xuelian Yishen granules effectively reduce proteinuria and improve renal function in elderly DKD patients with stages Ⅲ-Ⅳ and spleen-kidney qi deficiency pattern, with favorable therapeutic efficacy.