Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic digestive disease. Recent observational studies have reported that the Chinese herbal formula Huoxiang Zhengqi (HXZQ) can relieve IBS-D symptoms, but no high-level evidence is presented. Therefore, we want to evaluate the efficacy and safety of HXZQ for IBS-D patients.This is a double-blind, randomized, placebo-controlled trial. The 212 eligible patients with IBS-D will be randomly assigned to receive either HXZQ oral liquid or a placebo, at a 1:1 ratio, for 4 weeks with a 4-week follow-up period. Adequate relief will be the primary outcome measures. IBS symptom severity score, IBS quality-of-life questionnaire, EQ-5D-5L, and Chinese medicine symptom questionnaire will be the secondary outcome measures.This trial aims to demonstrate the efficacy and safety of HXZQ for IBS-D, which is expected to be an effective IBS-D treatment.The trial was registered with the Chinese Clinical Trial Registry, ChiCTR1900026837 . Registered on 24 October 2019.© 2021. The Author(s).