In this study, we investigated the protective effects of Ecklonia cava (E. cava, EC) against gluten-induced oxidative damage and inflammation in HaCaT cells, a human keratinocyte. First of all, the hot water extract prepared from EC (ECH) was used for this study. ECH treatment increased the cell viability of HaCaT cells, which was reduced by gluten stimulation, and inhibited the generations of intracellular reactive oxygen species (ROS) and nitric oxide (NO). Moreover ECH decreased the sub-G1 DNA contents and apoptotic body formation in gluten-stimulated HaCaT cells. The expression levels of inflammatory cytokines (interlukin (IL)-1β, IL-4, IL-5, IL-6, IL-8 and IL-13) were also decreased by ECH treatment. Furthermore, ECH decreased the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) by suppressing the activation of nuclear factor (NF)κB and ERK/P38 signaling in gluten-stimulated HaCaT cells. From theses results, we suggest that ECH possess the potential to attenuate oxidative damage and inflammation caused by gluten stimulation in HaCaT cells.