Helicobacter pylori is a major human pathogen that plays central roles in chronic gastritis and gastric cancer. Recently, we reported that auraptene suppressed H. pylori adhesion via expression of CD74, which has been identified as a new receptor for H. pylori urease. In this study, we attempted to clarify the effects of oral feeding of auraptene on H. pylori infection and resultant inflammatory responses in C57BL/6 mice and found that it remarkably attenuated H. pylori colonization and gastritis. Biochemical analyses revealed that auraptene inhibited H. pylori-induced expression and/or production of CD74, macrophage migration inhibitory factor, interleukin-1β, and tumor necrosis factor-α in gastric mucosa, together with serum macrophage inhibitory protein-2. It is notable that treatment with this coumarin during the pretreatment period was more effective than that during posttreatment. Our results suggest that auraptene is a promising phytochemical for reducing the risk of H. pylori-induced gastritis and carcinogenesis.