Interest in using foods to stimulate endogenous glucagon-like peptide-1 (GLP-1) has outpaced evidence that transient postprandial increases translate into meaningful physiological outcomes. This review critically examines how food processing and matrix architecture interact with digestion and microbial metabolism to determine the identity, timing, intestinal location, and epithelial accessibility of GLP-1-stimulating ligands. PubMed/MEDLINE, Web of Science Core Collection, BIOSIS Citation Index, and Scopus were searched for the relevant literature. Evidence from cellular systems, organoids, perfused intestines, animal models, and human studies indicates that sugars, amino acids, peptides, fatty acids, monoacylglycerols, bile acids, and microbial metabolites engage distinct nutrient-sensing pathways. However, GLP-1 responses depend not only on chemical composition but also on cellular integrity, particle size, viscosity, starch organization, emulsion structure, protein processing, fermentation, gastric emptying, and the site of intestinal release. These factors can modify the magnitude and kinetics of GLP-1 exposure, although effects vary considerably with material, dose, comparator, population, and experimental model. Whey-containing preloads provide the most consistent acute human evidence, whereas findings for fibres, emulsions, phytochemicals, fermented foods, and controlled-release approaches remain heterogeneous. Importantly, increases in circulating GLP-1 do not consistently coincide with reduced appetite or energy intake, improved glycaemia, or sustained changes in body weight. Food-induced GLP-1 secretion, reduced degradation through dipeptidyl peptidase-4 inhibition, and direct GLP-1 receptor agonism therefore represent distinct biological mechanisms. Overall, food structure can modestly and context-dependently modulate endogenous GLP-1 exposure, but current evidence does not support physiological or therapeutic equivalence with pharmacological GLP-1 receptor agonists.
