Gastric ulcers are a common gastrointestinal disease across the globe. Alcohol consumption is the primary cause of gastric carcinogenesis and progression. We investigated the gastroprotective effects of fermented lotus root (FL) against ethanol (EtOH)/HCl-induced gastric ulcers in a rat model and the conceivable underlying mechanisms involved. Rats received different doses of FL (50, 100, and 200 mg/kg) or ranitidine (positive control, 30 mg/kg) via oral gavage daily for 14 days. One hour after the last oral administration of FL, the EtOH/HCl mixture was orally intubated to induce gastric damage. Oral administration of FL significantly alleviated the gastric lesions. Moreover, FL also elevated the amounts of nitric oxide and the antioxidant enzyme activities of superoxide dismutase, glutathione peroxidase, and catalase in the stomach. To verify the gastric mucosal defense mechanism, inflammation-related genes were measured. Our results revealed that FL effectively inhibited gastric mucosal damage via downregulation of the nuclear factor-kappaB (NF-κB) response in the stomach. The administration of FL significantly lowered the gastric mRNA expression of inflammation-related genes, including NF-κb1, tumor necrosis factor-α, interferon γ, and prostaglandin-endoperoxide synthase 2, compared with the gastric ulcer control group. In addition, the NF-κB signaling pathway-related protein markers inhibitor of κB (IκB)-α, IκB kinase, and NF-κB were significantly reduced in the FL groups. Taken together, these data suggest that FL administration may have potential as an alternative treatment for gastric ulcers due to its antioxidant and anti-inflammatory effects and its ability to promote the recovery of gastric mucosa.