Peptic ulcer disease (PUD) presents a common challenge for both primary care providers and gastroenterologists, characterized by varied symptoms such as abdominal pain, nausea, vomiting, weight loss, and potentially severe complications like bleeding or perforation. Understanding the underlying risk factors and mechanisms driving PUD is crucial for effective diagnostic and treatment approaches. This study investigates the protective effects of the ethanolic extract of Sorghum bicolor leaves (EESBL) against ethanol-induced mucosal damage in Wistar rats. Nitrite levels, glutathione (GSH) levels, catalase concentration, and lipid peroxidation (MDA content) were evaluated to elucidate EESBL's mechanisms of action. In the vehicle-treated ethanol group, nitrite levels were significantly elevated, and GSH levels were reduced compared to sham controls. Treatment with EESBL effectively mitigated these changes, lowering nitrite levels and boosting GSH concentrations. Catalase levels were decreased in the ethanol-treated group but remained unchanged with EESBL treatment. Moreover, ethanol-induced lipid peroxidation, indicated by increased MDA content, was markedly reduced by EESBL. Morphological examination revealed that EESBL-treated rats exhibited fewer gastric lesions and preserved mucosal integrity compared to ethanol-only controls. These findings underscore the antiulcer properties of EESBL, suggesting its potential as a therapeutic agent for attenuating ethanol-induced gastric mucosal damage in clinical settings.