Chemical substances of foods drive the cognitive recognition of taste with the subsequent regulation of digestion in the gastrointestinal (GI) tract. Tastants like glutamate can bind to taste membrane receptors on the tip of specialized taste cells eliciting umami taste. In chemical-sensing cells diffused through the GI tract, glutamate induces functional changes. Most of the taste-like receptor-expressing cells from the stomach and intestine are neuroendocrine cells. The signaling molecules produced by these neuroendocrine cells either activate afferent nerve endings or release peptide hormones that can regulate neighboring cells in a paracrine fashion or travel through blood to their target receptor. Once afferent sensory fibers transfer the chemical information of the GI content to the central nervous system (CNS) facilitating the gut-brain signaling, the CNS regulates the GI through efferent cholinergic and noradrenergic fibers. Thus, this is a two-way extrinsic communication process. Glutamate within the lumen of the stomach stimulates afferent fibers and increases acid and pepsinogen release; whereas on the duodenum, glutamate increases the production of mucous to protect the mucosa against the incoming gastric acid. The effects of glutamate are believed to be mediated by G protein-coupled receptors expressed at the lumen of GI cells. The specific cell-type and molecular function of each of these receptors are not completely known. Here we will examine some of the glutamate receptors and their already understood role on GI function regulation. J. Med. Invest. 56 Suppl.: 209-217, December, 2009