To investigate the clinical effect of soothing the liver and strengthening the spleen therapy on diarrhea-predominant irritable bowel syndrome (IBS-D) of liver depression and spleen deficiency syndrome and its effect on serum brain-gut peptide level. Methods:Seventy patients with IBS-D were randomly divided into an observation group (n=35) and a control group (n=35). The control group was treated with conventional western medicine, and the observation group was provided additional self-made Shuganjianpi Decoction for treatment, both for 4 weeks. The levels of 5-serotonin (5-HT), calcitonin gene-related peptide (CGRP), serum substance (SP) and neuropeptide Y (NPY) in the 2 groups were compared before and after treatment, and the clinical effective rate and recurrence were analyzed. Results:After treatment, the level of serum 5-HT, CGRP, SP, NPY in both of the 2 groups were lower than before treatment, and those of the observation group was lower than those of the control group (P<0.01); The clinical symptoms integral of the 2 groups were lower than that before treatment, and the improvement of abdominal pain, diarrhea, abdominal distension and fatigue in the observation group were significantly gtreater than those in the control group (P<0.01); The total effective rate was 91.42% in the observation group, which was significantly higher than that in the control group (71.42%) (P<0.05). During follow-up, 2 cases (6.25%) relapsed in the observation group, while 8 (32%) in the control group and there was significant difference between the 2 groups (P<0.05). Conclusion:Shuganjianpi decoction combined with western medicine can significantly decrease the levels of serum 5-HT, CGRP, SP and NPY in patients with IBS-D, and improve clinical symptoms with a low relapse rate, showing good clinical efficacy.