Lactisole is an antagonist of sweet taste receptors, reducing both sweetness intensity and persistence. It blocks the activation of the sweet taste receptor T1R3 by natural and synthetic sweeteners and increases the inhibition of T1R2 by umami compounds. Lactisole can be used to explore the roles of these receptors in diverse pathways, including glucose-induced insulin secretion in pancreatic β-cells and the secretion of glucagon-like peptides by enteroendocrine L-cells.