OBJECTIVE: To evaluate the efficacy of combined otilonium bromide (OB) and trimebutine maleate (TM-906) therapy in patients with irritable bowel syndrome (IBS). METHODS: Data from 105 IBS patients treated at the Affiliated Hospital of Shaoxing University were retrospectively analyzed. Patients were divided into two groups: the control group (n=50), receiving OB alone, and the observation group (n=55), receiving both OB and TM-906. A comprehensive set of data, including treatment efficacy, safety profiles, clinical symptom improvements, serum markers, and quality of life, were collected from both groups. RESULTS: The observation group exhibited significantly higher treatment efficacy and greater improvement in quality of life compared to the control group (P<0.05). The incidence of adverse reactions was similar between groups (7.27% vs. 6.00%, P>0.05). Additionally, the observation group experienced faster symptom relief and a more substantial reduction in inflammatory markers post-treatment (P<0.05). CONCLUSIONS: Combined therapy with OB and TM-906 is a safe and effective treatment for IBS, offering quicker symptom relief and substantial improvement in quality of life.