OBJECTIVE: To explore the efficacy of Jianpiyangxue granules on gastrointestinal autonomic nerve dysfunction and their impact on adverse reactions. METHODS: From September 2016 to September 2020, 120 patients with gastrointestinal autonomic nerve dysfunction treated in our hospital were retrospectively selected and randomly assigned to a treatment group (TG) which was administered Jianpiyangxue granules prepared by our hospital and a control group (CG) which was administered routine Western medicine treatment (B vitamins + oryzanol). There were 60 patients in each group. The clinical efficacy and incidences of adverse effects were compared between the groups. The gastrointestinal hormone indexes, the inflammatory cytokines, and the immune indexes were analyzed before and after the therapy. The gastrin (GAS) and motilin (MTL) levels were measured using the motilin stimulating method, and the somatostatin (SS) levels were measured using ELISA for comparison. The autonomic nerve dysfunction symptoms were used for the evaluation. The degree of neurological functional defects scale (NIHSS) was used to assess the neurological functional defect levels. The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were used to assess the patients' psychological statuses. RESULTS: After the therapy, the GAS, MTL, and SS expressions in the TG were remarkably higher than they were in the CG. The CRP and IL-6 expressions in the TG were significantly lower than they were in the CG. The TG had higher IgG, IgM, and IgA levels as compared with the CG, higher grade 0 and grade 1 scores on the gastrointestinal autonomic nerve dysfunction, but lower grade 2 and 3 scores were observed compared to the CG. Significantly lower NIHSS, SAS, and SDS scores were recorded in the TG compared with the CG. The TG yielded more promising outcomes in terms of the total effective rate and the incidences of adverse reactions than the CG. CONCLUSION: Jianpiyangxue granules contribute to enhancing the clinical efficacy, reducing the incidence of adverse reactions, and improving the gastrin, somatostatin, and other indicators in treating gastrointestinal autonomic nerve dysfunction.