Objective: To explore the therapeutic effect of Shengyang Yiwei Decoction in patients with diarrhea-predominant irritable bowel syndrome (IBS) due to spleen and stomach weakness. Methods: 40 patients with diarrhea-predominant IBS who were treated from April 2018 to April 2020 were taken as samples. TCM (traditional Chinese medicine) syndrome differentiation found that they were all due to spleen and stomach weakness. They were randomly divided into two groups. Group A was treated with modified prescriptions of Shengyang Yiwei Decoction, while Group B was treated with Western medicine. The therapeutic effects in the two groups were compared. Results: The treatment efficacy in Group A was higher than that in Group B (P < 0.05); the symptom scores of Group A such as loose stools, chills, physical weakness, poor appetite, and abdominal distension after meals were all lower than those in Group B (P< 0.05); the SF-36 (36-Item Short Form Health Survey) scores of patients with diarrhea-predominant IBS in Group A were higher than those in Group B (P < 0.05); the treatment satisfaction of Group A was higher than that of Group B (P< 0.05). Conclusion: Treatment of diarrhea-predominant IBS patients with spleen and stomach weakness by Shengyang Yiwei Decoction can promote the disappearance of gastrointestinal discomfort symptoms, improve the quality of life, and enhance treatment efficacy. Hence, it is an efficient and feasible treatment for diarrhea-predominant IBS due to spleen and stomach weakness.