ETHNOPHARMACOLOGICAL RELEVANCE: Mukta Pishti (MKP) is a traditional Ayurvedic medicine described in classical textbook 'Rasatarangini' and synthesized from marine pearls following classical methodology. MKP is used as therapeutic medicine against hyperacidity, irritable bowel syndrome, and gastric ulcers. AIM OF THE STUDY: Here, we explored the therapeutic properties of MKP in alleviating peptic ulcer in male Wistar rat model of pylorus ligation. METHODS: Physicochemical properties of MKP were explored using scanning electron microscope, electron dispersive X-ray, dynamic light scattering, and Fourier-transform-infrared (FTIR)-spectroscopy analysis. Animals were orally treated twice daily with dosages of MKP, over a period of 15 days. The animals underwent 6 h pylorus ligation for the induction of peptic ulcers and analyzed for biochemical changes in gastric content, gross and histopathological changes in the stomach region. RESULTS: Physicochemical analysis showed 0.1-30 μm particles size for MKP, with elemental composition of oxygen, calcium, silica, carbon, phosphorus, and sodium. FTIR-spectroscopy indicated presence of aragonite crystals in MKP with capability of physically binding to gastric mucin molecules. Additionally, MKP treatment modulated gastric pH in simulated digestion model but did not affect the overall gastric content and total/free acidity levels in the in vivo pylorus ligation model. However, MKP treatment in rats significantly reduced ulcer index in stomach region and protected it against epithelial damages, hemorrhages and edema induced by pylorus ligation. CONCLUSION: MKP alleviated peptic ulcer induced by pylorus ligation in the male Wistar rats. Further research is warranted to elucidate the precise mode of action and long-term safety of Mukta Pishti.