Gastric acid has been a major pathogenic factor in peptic ulcer diseases thus, the suppression of acid secretions is a key therapeutic target for gastric ulcers, which includes the use of proton pump inhibitors, antacids, targeting gastrin receptors and histamine receptors antagonists. In this study, the acute toxicity, phytochemistry, antisecretory activity, histopathology and proton pump (H+/K+-ATPase) inhibitory potential of the aqueous, methanol and hexane leaves extracts of Saccharum spontaneum Linn. were evaluated on the stomach of Wister albino rats. Aspirin induced gastric ulcer generated as lesions, from pin-point craters to larger eruptions and the dose-dependent effectiveness of the extracts were assessed and methanol extract was found to be significantly most effective (P<0.05). Acute oral toxicity for the aqueous, methanol and hexane extracts of the leaves of S. spontaneum showed that the extracts were relatively safe with an LD50 value greater than 5000 mg/kg body weight with no lethal effect in rats. Preliminary Phytochemical studies of the extracts revealed the presence of alkaloids, triterpenes, glycosides, saponins, steroids, flavonoids, tannins and phenols. All the extracts (200 mg/kg and 400 mg/kg) exhibited a high antisecretory effect as it significantly (P<0.05) lowered the lesion index induced by aspirin, reduced the volume of gastric juice, free and total acidity with a consequent rise in gastric pH as compared to the ulcer group. The methanol extract showed the highest antiulcer activity with a percentage inhibition of 65.22% when compared to the standard control (73.91%). Histopathological examination of rats gastric mucosa showed mild abrasion on the lining epithelium with no mucosal necrosis and hemorrhage, with the methanol extract exhibiting a better cytoprotection against gastric mucosal damage. The methanol extract also inhibited the H+/K+- ATPase activity with IC50 value of 116.41 ± 41.98 μg/ml compared with omeprazole with