Glutamate (Glu), either as one of the amino acids of protein or in free form, constitutes up to 8–10% of amino acid content in the human diet, with an intake of about 10–20 g/day in adults. In the intestine, postprandial luminal Glu concentrations can be of the order of mM and result in a high intra-mucosal Glu concentration. Glu absorbed from the intestinal lumen is for a large part metabolized by enterocytes in various pathways, including the production of energy to support intestinal motility and functions. Glu is the most important fuel for intestinal tissue, it is involved in gut protein metabolism and is the precursor of different important molecules produced within the intestinal mucosa (2-oxoglutarate, L-alanine, ornithine, arginine, proline, glutathione, γ-aminobutyric acid [GABA]). Studies in adult humans, pigs, piglets or preterm infants indicate that a large proportion of Glu is metabolized in the intestine, and that for the usual range of Glu dietary intake (bound Glu and free Glu including added Glu as a food additive in normal amounts up to 1 g/day), circulating Glu is tightly maintained at rather low concentrations. Systemic blood levels of Glu transiently rise when high doses monosodium glutamate (> 10–12 g), higher than normal human dietary consumption, are ingested and normalize within 2 h after the offset of consumption. Glu is also involved in oral and post oral nutrient chemosensing that involves gustatory nerves and both humoral and neural (vagal) gut-brain pathways with an impact on gut function and feeding behavior. Glu functions as a signaling molecule in the enteric nervous system and modulates neuroendocrine reflexes in the gastrointestinal tract. The oral taste sensation of Glu involves its binding to the oral umami taste receptors that triggers the cephalic phase response of digestion to prepare for food digestion. Glu is sensed again in the gut, inducing a visceral sensation that enhances additional gut digestive processes through the visceral sense (vago-vagal reflex).