Excessive alcohol consumption harms the human body, particularly the digestive system, by causing damage to the gastric mucosa. Tea saponin is a natural active substance extracted from tea tree seeds that has gastroprotective potential against alcohol-induced mucosal damage. However, the protective mechanism of tea saponins is not fully understood. The current study aimed to explore the protective mechanism of tea saponins against alcohol-induced gastric mucosal injury in mice. Histopathological changes, immunohistochemistry, immunoblotting, and gastric mucosa-related cytokine levels were analyzed in three groups of male mice: model, control, and tea saponin-treated. Compared to the model group, the tea saponin group prominently ameliorated alcohol-induced gastric mucosal injury by improving cell necrosis, inflammatory cell infiltration, and edema. Downregulation of inflammation-related factors cluster of differentiation 68 (CD68), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) was also found in the tea saponin group. These results suggest that tea saponins have a protective effect against alcohol-induced gastric mucosal damage in mice. Therefore, tea saponin may serve as a food additive for gastric mucosal protection.