Acrostichum aureum Linn., a medicinal pteridophyte growing in mangrove forests and coastal regions of tropical and subtropical areas worldwide, has been proved to possess various biological effects. However, the protective effect of Acrostichum aureum Linn. against gastric ulcer still remains unidentified. Therefore, the gastroprotective effect of the water extract of Acrostichum aureum Linn. (WEAC) was investigated in ethanol-induced gastric injury model. According to our results, pretreatment with WEAC (100, 200, and 400 mg/kg) could dramatically decrease the ulcer areas and ameliorate the pathological damage induced by alcohol in rat's gastric tissues. In addition, WEAC administration prevented the stomach from oxidative damage via markedly increasing the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and decreasing the malondialdehyde (MDA). Besides, WEAC pretreatment alleviated inflammatory infiltration by reducing the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as decreasing the protein expressions of phosphorylation of IκBα and p65. Taken together, WEAC exerted potential therapeutic efficacy for gastric ulceration, and this may be involved in the suppression of oxidative stress and inflammatory response.