NSAIDs are the most commonly recommended pain reliever and have been widely associated with the formation of gastric ulcers and mucosal injuries. In contrast, grape seed extract (GSE), rich in polyphenolic compounds renowned for their anti-inflammatory and antioxidant attributes, holds significant promise in counteracting ulcer formation. The trial encompassed an efficacy assessment conducted on laboratory rats, serving to appraise the gastroprotective potential of GSE. The experimental timeline spanned 15 days, during which diverse dosages of GSE, alongside the standard drug omeprazole, were administered to distinct groups of rats. The subjects were compartmentalized into five groups, denoted as G0 (control), G1 (standard drug), G2 (100mg/Kg GSE), G3 (200mg/Kg GSE), and G4 (300mg/Kg GSE). Gastric ulcers were induced using Indomethacin. Subsequent to the experimental regimen, various stomach parameters, encompassing gastric pH, gastric juice volume, total gastric acidity, ulcer index, and ulcer inhibition percentage, were meticulously evaluated. Complementary biochemical assessments were conducted to ascertain key biomarkers including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase. The findings incontrovertibly affirmed the beneficial impact of grape seed extract in mitigating gastric ulcers. Furthermore, the outcomes underscored the dose-dependent influence of the extract on pertinent variables such as gastric pH, total gastric acidity, gastric volume, ulcer index, and ulcer inhibition percentage. Pertinently, the biochemical analyses unveiled a progressive augmentation of antioxidant biomarkers—glutathione, superoxide dismutase, and catalase—alongside a concurrent reduction in malondialdehyde levels within the bloodstream. So, from the results, it is evident that grape seed extract exhibits gastroprotective potential against gastric ulcers.