Gastric ulcer is a prevalent gastrointestinal disorder caused by excessive gastric acid secretion, impaired mucosal defense and Helicobacter pylori infection. Existing pharmacological therapies such as proton pump inhibitors and H<inf>2</inf>-receptor antagonists, face challenges like resistance and adverse effects. Given the increasing need for safer and more effective antiulcer agents, investigating plant-derived compounds offers a promising alternative. The potential of plant extract in modulating gastric acid secretion and enhancing mucosal defense mechanisms warrants systematic evaluation. Garcinia gummi-gutta, a tropical fruit known for its medicinal properties, has shown potential antiulcer activity. This study evaluates the ethanolic extract of Garcinia gummi-gutta (EEG) fruit for its gastroprotective effects. The study involved the EEG effect on enzyme inhibition assay evaluated by H�/K�-ATPase activity. Various assessments including gastric pH, total acidity, gastric wall mucus levels, histamine content in the gastric mucosa and gastric volume, were experimented on ulcer-induced animal models across nine groups. The EEG extract demonstrated potent enzyme inhibition, with inhibition rates increasing from 54.41 at 10 μg/mL to 90.89 at 500 μg/mL, confirming its efficacy in reducing gastric acid secretion. Animal studies revealed dose-dependent ulcer protection, with 500 µg/mL of EEG providing appreciable ulcer prevention supporting histopathological studies. Lower doses (10-250 µg/mL) showed moderate effects. The findings suggested that EEG extract is a promising natural alternative for ulcer management, warranting further clinical investigations to explore its therapeutic potential. © 2025 Elsevier B.V., All rights reserved.