ABSTRACT: Over the years, management of advanced peptic ulcers used to be a nightmare and in most cases surgery is resorted to. This study was carried out to investigate the anti-ulcer activities of the oil extract of Balanites aegyptiaca seed in guinea pigs. Thirty guinea pigs weighing between 200 and 440.8 g were randomly assigned into six groups of five each. Gastroduodenal ulceration was achieved by pyloric ligation and histamine injection. The anti-ulcer effect of the oil was compared with omeprazole (10 mg/kg body weight) given orally. The oil extract of B. aegyptiaca seed did not significantly reduce the mean severity of ulcer incidence in both pyloric ligation and in histamine injection ulcer models. But it significantly (P≤0.05) decreased the volume of gastric secretion in histamine injection model. It equally decreased the percentage of ulcer incidence in the guinea pigs and raised the percentage protection in both models of experiment by 40.9 and 50.6%, respectively. However, omeprazole at the dose rate of 10 mg/kg body weight gave better protection of 80.3 and 84.4% against ulcer in both models, respectively. The results showed that B. aegyptiaca oil possessed moderate gastric anti-secretory and cytoprotective properties which can be employed in the prevention, treatment and relief of gastric ulcer symptoms.