γ-PGA is a major ingredient of “natto”, a Japanese traditional fermented food, and “Chungkookjang” a Korean fermented seasoning, both made from soybeans6 and used for dietary consumption. In the present study, we investigated whether γ-PGA, a non-LPS TLR4 ligand, could activate TLR4 signaling when administered orally. Our results demonstrate the induction of IFN-β by peroral administration of γ-PGA without the production of proinflammatory cytokines, thereby establishing an antiviral state against mouse norovirus. We provide evidence of in vivo efficacy of γ-PGA in limiting norovirus infection, highlighting the potential of γ-PGA as a prophylactic antiviral agent.