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(1) Background: Irritable bowel syndrome (IBS) is a common disease, with multiple pathophysiological mechanisms involved. A single treatment for all the patients with IBS is not possible. Prebiotics may have a beneficial effect on IBS patients with constipation. (2) Methods: A randomized cross-over case-control study was conducted, including patients with IBS and constipation (IBS-C), who were randomized into two groups receiving a specific constipation diet with or without a food supplement containing inulin, choline and silymarin (Stoptoxin®, Fiterman Pharma, Iasi, Romania). Patients were evaluated at baseline, after four and eight weeks, using a questionnaire to assess IBS symptoms. (3) Results: 51 IBS-C patients were included, of which 47 patients finished the trial (33 women, mean age 52.82 years). Adding Stoptoxin® to a diet for constipation brought extra benefits. Abdominal pain severity improved by 68.3% after the diet and Stoptoxin® (p = 0.004) and abdominal bloating severity parameter improved by 34.8% (p = 0.040). The stool number per week and the stool consistency according to the Bristol scale were improved, but without statistical significance between groups (p > 0.05). (4) Conclusions: The combination of inulin, choline and silymarin associated with a specific-constipation diet had obvious clinical beneficial effects on IBS-C patients in terms of bowel movement, abdominal pain and bloating. [ABSTRACT FROM AUTHOR]