BACKGROUND: Irritable Bowel Syndrome (IBS) leads to significant impairment of health-related quality of life, for the alleviation of which, the efficacy of available therapies is modest. Limited data is available on the role of Saccharomyces cerevisiae in treating patients with IBS. METHODS: Thirty patients with IBS as per Rome-IV criteria, visiting our outpatient department from March 2021 to October 2021, were given capsule Saccharomyces cerevisiae 500 mg twice daily for four weeks. Evaluation for abdominal pain symptoms was done every week and the patient's compliance was assessed. IBS Quality of Life (QOL) questionnaires were filled at baseline and after four weeks of treatment. The QOL and pain scales were adjusted to 0-100 for statistical analysis. RESULTS: Seventeen patients (56.7%) were males. The age range was 21-72 years (mean ± SD: 39. 63 ± 14.32), out of which 18(60%) patients were 20-40 years old. Body Mass Index (BMI) ranged from 18-33 (25.33 ± 4.09), and 17 (56.67%) were overweight or obese. Sixteen patients had constipation predominant (53.3%), nine had diarrhea-predominant (30%), and five had mixed-type (16.7%) IBS. There was an improvement in the pain score from 63.81 at week 0 (W0) to 20.48 at the end of week 4 (W4) (p<0.001). An improvement was noted in all the eight categories of IBS QOL questionnaire, i.e., dysphoria (p<0.001), interference with activity (p<0.001), body image (p<0.001), health worry (p<0.001), food avoidance (p<0.001), social reaction (p<0.001), sexual function (p<0.001) and relationships (p<0.001). There was an overall improvement in QOL score from a mean of 24.68 at baseline to 58.09 at the end of the study duration (p<0.001). The improvement in the pain score showed a positive correlation with the improvement in quality of life (p<0.001). CONCLUSION: Treatment with Saccharomyces cerevisiae improved the pain and quality of life in patients with IBS and it appears to be a promising option for alleviating symptoms in these patients.