The present study investigated the effect of berberine (BBR) combined with probiotics on the treatment of IBS and the control of inflammatory response (IR). Patients with IBS were selected as subjects and divided into two groups: BBR combined with probiotics treatment group and BBR single drug treatment group. Clinical efficacy, remission, inflammatory factors, gastrointestinal hormone levels, serum neuropeptide Y (NPY), 5-hydroxytryptamine (5-HT) levels, adverse reactions (ADs), intestinal symptoms and quality of life in 2 groups were observed. The study demonstrated that G was more effective than CG. The IL-I8, IL-23, TNF-alpha, vasoactive intestinal peptide (VIP), somatostatin (SS) and 5 HT were decreased in both the groups. Motilin and NPY were higher in RG than in CG. There was no significant difference in the incidence of ADs between the two groups, but the IBS intestinal symptom Severity Scale (IBS-BSS) and IBS Quality of Life Scale (IBS-QOL) scores in RG group were lower than those in CG group. In summar3, BBR combined with probiotics inhibits IR in patients with significant efficacy, which is worthy of clinical promotion.