To explore the clinical effect of Shenkang Decoction in chronic renal failure (CRF) patients with hemodialysis (HD). From November 2020 to December 2021, a total of 160 patients with CRF, who received HD, were included as the research objects, and they were divided into a reference group and a treatment group by random number table method (80 cases in each group). The former group was given basic drug treatment, and the latter group was given Shenkang decoction treatment at the same time as basic drug treatment. The renal function indexes, Traditional Chinese Medicine (TCM) syndrome scores, nutritional status, dialysis adequacy, treatment efficiency, and adverse reactions, were compared between the two groups. After treatment, the patients in the treatment group had lower levels of creatinine and blood urea nitrogen, lower TCM syndrome scores, and higher levels of various nutritional status indicators than the reference group (p < 0.05). After treatment, the effective rate of the treatment group was higher compared with the reference group (p < 0.05). There was no significant difference between the two groups of dialysis adequacy index (p > 0.05). No adverse reaction was found in the two groups of patients in routine urine, blood, stool, liver, and kidney function tests, and electrocardiogram monitoring. Shenkang decoction applied to CRF and HD patients can significantly improve clinical symptoms and renal function, maintain a good nutritional status and little impact on dialysis adequacy, and improve life quality with significant curative effect, high safety, and little adverse reactions.