Odorant receptors (ORs) detect volatile molecules and are naturally expressed in the membranes of olfactory epithelial cells. However, recent studies have shown that odorant (olfactory) receptors are also expressed throughout the body in different tissues, including the kidney, brain, sperm cells, skin, prostate, and gut. We recently demonstrated the functional expression of human ORs in cultured human fungiform taste (HBO) cells. In this study, we aimed to explore the signal transduction pathway activated by the odor, indole, in HBO cells. Indole has a flowery odor at low concentrations and a fecal odor at higher concentrations. Using single-cell calcium imaging, indole induced transient intracellular calcium signals in HBO cells by activating an adenylyl cyclase signaling pathway. In addition to the canonical olfactory signaling pathways, several transient receptor potential cation channels (TRPs) such as TRPA1 and TRPV1 were also implicated in indole-induced responses. These results confirm the presence of similar odor-mediated signal transduction pathways in both human taste cells and olfactory cells. In addition, these data suggest that HBO cells can be used to screen a variety of odorants against chemosensory receptors. This platform provides a mechanistic approach for identifying receptor agonists and antagonists that can be used to produce novel odors eliminate malodors.