Background: Numerous pharmacologically beneficial compounds have been isolated from natural products derived from plants; these compounds are often characterized as phytochemicals and are used in flavors, spices, fragrances, and colors. In the current study, we aimed to obtain novel immunomodulators from aroma compounds. Methods: We selected a candidate that inhibits antigen-presenting cell-mediated activation of T cells from an aroma library. The molecular mechanisms by which the candidate compound modulates immunoresponses were analyzed with in vitro studies, and the biological significance of the candidate was evaluated by using a mouse model. Results: b-Damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-dependent T cell activation, through 2-step screening using OT-II splenocytes. Investigations using flow cytometry, ELISA, and qPCR revealed that b-damascone inhibited dendritic cell (DC)-related responses, including DC-induced Th1 development, TLR ligand-induced transactivation and production of inflammatory cytokines in DCs, and LPS-induced upregulation of MHC class II and CD86 on DCs. Regarding intracellular events, we found that b-damascone treatment increased the levels of NRF2 protein and Hmox1 mRNA in DCs. Nrf2 -/- DCs, in which b-damascone-induced Hmox1 transcription was not observed, possessed Th1-induction activity and higher IL-12p40 production activity even in the presence of b-damascone in comparison with Nrf2 +/- DCs. Finally, we evaluated the effect of orally administered b-damascone on the pathology of contact hypersensitivity model mice and found that b-damascone intake suppressed ear swelling. Conclusions: The rose aroma compound b-damascone, which suppresses DC-mediated immunoresponses by activating the NRF2 pathway, could be useful to ameliorate immunorelated diseases.