Objective To explore the clinical efficacy of Shen'an decoction in treating chronic renal insufficiency and systematically assess its effects on immune regulation, renal function and lipid metabolism. Methods A prospective randomized controlled study was conducted, and 102 patients with chronic renal insufficiency were selected. Patients were randomly divided into the control group (51 cases, receiving conventional Western medical treatment) and the observation group (51 cases, receiving conventional Western medical treatment combined with Ren'an decoction). The traditional Chinese medicine (TCM) syndrome scores, clinical efficacy, levels of immunoglobulin (Ig) G, IgM, IgA, 24-hour urine protein quantification (24 hUP), cystatin C (Cys C), serum creatinine (Scr), blood calcium, blood phosphorus, triglycerides (TG) and total cholesterol (TC) were evaluated before treatment and 8 weeks after treatment. The levels of reactive oxygen species (ROS) and advanced oxidation protein products (AOPPs) were measured by enzyme-linked immunosorbent assay (ELISA). Adverse reactions such as nausea, diarrhea, dizziness and rash during the treatment period were recorded. Results After 8 weeks of treatment, the TCM syndrome scores, 24 hUP, Cys C, Scr, blood phosphorus, TG, TC, ROS and AOPPs were significantly lower in both groups than those before treatment, and the observation group was significantly lower than that of the control group (P<0.05). The levels of IgG, IgM, IgA and blood calcium were significantly higher in both groups than those before treatment, and the observation group was significantly higher than those of the control group (P<0.05). The total clinical effective rate of the observation group was higher than that of the control group (94.12% vs. 80.39%, P<0.05). There was one case of nausea, one case of dizziness and one case of rash in the observation group, and one case of nausea, one case of diarrhea and two cases of dizziness occurred in the control group. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion The addition of Shen'an decoction in the treatment of patients with chronic renal insufficiency on the basis of conventional Western medical treatment can improve the clinical efficacy, enhance immune function, renal function, lipid metabolism and oxidative stress indicators, with good safety.