Background: Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. Several species of Spondias are used in traditional medicine for the treatment of gastrointestinal diseases, infections, and inflammation, among other conditions. Objectives: The aim of this study was to investigate the antioxidant properties in vitro and gastroprotective effect in mice of the methanolic extract of branches of Spondias tuberosa (MEB). MEB was screened for antioxidant activities using different methods. Materials and Methods: Measurements of total phenolic compounds, flavonoids, and tannins were also evaluated. The profile of phenolic compounds of extract was performed by high-performance liquid chromatography (HPLC). MEB was investigated for acute and chronic toxicity and gastroprotective effects against ethanol-induced lesions in Swiss mice. Results: The extract showed antioxidant activity in vitro and high content of phenolic compounds, flavonoids, and tannins. The HPLC results identified the presence of gallic acid, chlorogenic acid, caffeic acid, and t-ferulic acid. The MEB showed no acute and chronic toxicity and in doses of 50, 100 and 200 mg/kg, v. o., reduced the area of ulcerative lesions induced by ethanol in 73.74, 72.02, and 72.40', respectively. Conclusion: The oral treatment with the extract of S. tuberosa branches (MEB) showed gastroprotective and antioxidant activities.