γδ T cells play an important role in anti‐infective immunity. The major subset of human γδ T cells selectively recognizes phosphorylated bacterial metabolites of the isoprenoid biosynthesis pathway, so‐called phosphoantigens. The activation of γδ T cells is modulated by functionally expressed innate immune receptors, notably Toll‐like receptor 2 and 3. It was also reported that in vitro expanded γδ T cells respond to muramyl dipeptide (MDP), the minimal peptidoglycan motif activating the nucleotide‐binding oligomerization domain containing 2 (NOD2) receptor, although it is unknown whether ex vivo isolated human γδ T cells express functional NOD2. Here, we report that freshly isolated, highly purified peripheral blood γδ T cells express NOD2 mRNA and detectable amounts of NOD2 protein. The biologically active MDP L‐D isomer but not the inactive D‐D isomer augmented the interferon‐γ (IFN‐γ) secretion in phosphoantigen‐stimulated peripheral blood mononuclear cells. Moreover, a moderate but reproducible and statistically significant increase in IFN‐γ secretion was also observed when highly purified peripheral blood γδ T cells were activated by T cell receptor cross‐linking in the presence of MDP. Taken together, our results indicate that in addition to the T cell receptor and Toll‐like receptors, circulating human γδ T cells express NOD2 as a third class of pattern recognition receptor for sensing bacterial products.