Background: Grahani Roga is a chronic gastrointestinal disorder described in Ayurveda as a consequence of Agnidushti (impaired digestive fire), leading to Ama formation and dysfunction of Grahani. Clinically, it resembles Irritable Bowel Syndrome (IBS), a functional bowel disorder associated with altered bowel habits and psychological stress. Manasika Bhavas such as Chinta, Shoka, Bhaya, and Krodha play a significant role in disturbing Agni and gut function. Objectives: To evaluate the role of Manasika Bhavas in the etiopathogenesis of Grahani Roga (IBS) and to assess the therapeutic efficacy of Mustakadi Churna and Brahmi Vati in its management. Materials and Methods: An open-label randomized clinical trial was conducted on 30 patients diagnosed with Grahani (IBS) as per classical features and Rome IV criteria. Patients aged 18–50 years were administered Mustakadi Churna (4 g twice daily before food with honey) and Brahmi Vati (500 mg, 2 tablets after food) for 30 days. Assessment was based on subjective parameters (bowel habits, abdominal pain, anorexia, bloating, udgara) and Manasika parameters (Chinta, Shoka, Bhaya, Krodha, Avasada, Udvega), along with objective investigations. Statistical analysis was performed using Wilcoxon signed-ranktest. Results: Statistically significant improvement (p<0.05) was observed in major gastrointestinal symptoms with an average improvement of 67.38%. Significant relief was also noted in psychological parameters such as Chinta (60.34%), Krodha (66.67%), and Udvega (66.67%). Overall, 20% patients showed marked improvement, 73.33% moderate improvement, and 6.67% mild improvement. No adverse effects were reported during the study. Conclusion: The study suggests that Grahani is a psychosomatic disorder involving Agnidushti and gut–brain axis imbalance. Combined therapy with Mustakadi Churna and Brahmi Vati effectively improves digestive function and mental well-being, providing a safe, holistic, and cost-effective approach in the management of Grahani (IBS).