Abstract Diallyl disulfide (DADS) is a major organosulfur compound found in garlic oil that is widely used as a flavoring agent. In this study, we evaluated the effects of DADS on airway inflammation using an ovalbumin-induced model of allergic asthma and RAW264.7 cells. DADS decreased nitric oxide production with a reduction in the levels of interleukins (IL)-1β and IL-6 in RAW264.7 cells stimulated with LPS. DADS also reduced the expression of proinflammatory proteins including inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and matrix metalloproteinase (MMP)-9, and it enhanced the expression of antioxidant proteins including Nrf-2 and hemeoxygenase (HO)-1. In in vivo experiments, DADS decreased the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) with IL-4, IL-5, IL-13, and immunoglobulin (Ig) E. These results were consistent with the histological analysis. DADS attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, DADS induced the activation of Nrf-2 and the expression of HO-1. In contrast, DADS reduced the activation of NF-κB, iNOS and MMP-9. In conclusion, DADS reduced the airway inflammation via regulation of Nrf-2/HO-1 and NF-κB. These results suggest that DADS might represent a useful new oral therapy to treat allergic asthma.