Introduction: Irritable bowel syndrome (IBS) is a part of the larger group of functional gastrointestinal (GI) disorders that despite differences in location and symptom patterns share common features with regard to their motor and sensory physiology and central nervous system relationships. It generates a significant health care burden and can severely impair quality of life. It is characterized by symptoms of abdominal pain and discomfort that is associated with disturbed defecation. Ayurveda compares the symptoms of IBS with some of the diseases like Grahani, Kaphaja Pravahika, Shokaja Atisara, Bhayaja Atisara, etc. Bilvadi Leha and Kutajarishta are two common Ayurvedic formulations that are currently used for the management of such diseases. However, the safety of these drugs was not evaluated until now. Objective: Analysis of clinical safety and efficacy outcomes of Bilvadi Leha and Kutajarishta in IBS generated through multicenter open-label clinical studies at different CCRAS centers. Materials and methods: Analysis of data collected from two different clinical studies was critically evaluated. Safety assessments were done through analyzing liver function tests (LFTs), alanine aminotransferase, aspartate aminotransferase, serum alkaline phosphatase, serum protein, albumin, globulin, and bilirubin, and kidney function tests (KFTs) before and after the trial period. Paired sample t-test was used for comparison. A p-value < 0.05 was considered significant. Drug compliance and adverse drug reaction/adverse events, if any, were noted. Conclusion: The analysis of two different clinical studies clearly reveals that Bilvadi Leha and Kutajarishta are clinically safe, effective, and tolerable.