The review discusses the cellular mechanisms underlying incretin hormone secretion, focusing on GLP-1 and GIP, which play key roles in glucose homeostasis and appetite regulation. Enteroendocrine cells (EECs) in the gastrointestinal tract sense nutrients and secrete various hormones, including GLP-1 and GIP. These hormones are involved in regulating insulin secretion, appetite, food intake, and body weight. Modulating EEC hormone release could offer new therapeutic approaches for obesity and type 2 diabetes without surgery. The review highlights the complex signaling pathways involved in EEC function, including ion channels, nutrient transporters, and G-protein-coupled receptors (GPCRs). It also discusses the role of various GPCRs, such as FFAR1, FFAR4, GPR84, and GPR119, in sensing nutrients like fatty acids, bile acids, and short-chain fatty acids (SCFAs). Additionally, the review covers the role of taste receptors, such as TAS1R and TAS2R, in sensing sweet and bitter compounds, and the importance of transporters like SGLT1 and PEPT1 in nutrient sensing. The review also discusses the interactions between EECs and other cell types, such as D-cells (which secrete somatostatin) and the influence of other hormones and factors on incretin secretion. The review concludes that understanding the mechanisms of EEC function is crucial for developing new therapies for metabolic diseases.The review discusses the cellular mechanisms underlying incretin hormone secretion, focusing on GLP-1 and GIP, which play key roles in glucose homeostasis and appetite regulation. Enteroendocrine cells (EECs) in the gastrointestinal tract sense nutrients and secrete various hormones, including GLP-1 and GIP. These hormones are involved in regulating insulin secretion, appetite, food intake, and body weight. Modulating EEC hormone release could offer new therapeutic approaches for obesity and type 2 diabetes without surgery. The review highlights the complex signaling pathways involved in EEC function, including ion channels, nutrient transporters, and G-protein-coupled receptors (GPCRs). It also discusses the role of various GPCRs, such as FFAR1, FFAR4, GPR84, and GPR119, in sensing nutrients like fatty acids, bile acids, and short-chain fatty acids (SCFAs). Additionally, the review covers the role of taste receptors, such as TAS1R and TAS2R, in sensing sweet and bitter compounds, and the importance of transporters like SGLT1 and PEPT1 in nutrient sensing. The review also discusses the interactions between EECs and other cell types, such as D-cells (which secrete somatostatin) and the influence of other hormones and factors on incretin secretion. The review concludes that understanding the mechanisms of EEC function is crucial for developing new therapies for metabolic diseases.