Aim: The objective of the current study was to evaluate the antioxidant, anti-inflammatory, and anti-ulcerogenic properties of flaxseed, pumpkin, and lupin seed oils, adopting an indomethacin-induced gastric ulceration rat model. Gastric ulcers were generated in Sprague Dawley rats by a single indomethacin oral dose. The tested oils and famotidine were orally administrated for 15 days before ulcer induction. Results: Flaxseed, pumpkin, and lupin seed oils pretreatment attenuated gastric ulcers, as evidenced by the notable reduction in the total acidity, gastric juice volume, and ulcer index, and the increase in gastric pH and the preventive index in addition to restoring gastric levels of PGE-2, nitric oxide, and COX-2 levels. Furthermore, the tested oils significantly prevented the upsurge in gastric TNF-⍺ and IL-1β and enhanced the serum antioxidant capacity with concomitant reduction in oxidant capacity. Histopathological findings supported these results. The prophylactic effects of the tested oil are possibly ascribed to its varied bioactive substances and the free radicals scavenging activities, which we have demonstrated in the in vitro study. Conclusion: Flaxseed, pumpkin, and lupin oils exhibited a potential gastroprotective effect against the ulcerative effects of indomethacin. Their effects may be mediated by suppressing oxidative stress and gastric inflammation and maintaining gastric PGE-2, nitric oxide, and COX-2 levels.