Glucagon-like peptide-1 (GLP-1) is a cell type-specific post-translational product of proglucagon. It is encoded by the proglucagon gene and released primarily from intestinal endocrine L-cells in response to hormonal, neuronal, and nutritional stimuli. In addition to serving as an incretin in mediating the effect of meal consumption on insulin secretion, GLP-1 exerts other functions in pancreatic islets, including regulation of β-cell proliferation and protection of β-cells against metabolic stresses. Furthermore, GLP-1 exerts numerous other functions in extrapancreatic organs, whereas brain GLP-1 signaling controls satiety. Herein we review the discovery of two incretins and the development of GLP-1-based drugs. We also describe the development of cellular models for studying mechanisms underlying GLP-1 secretion over the past 30 years. However, the main content of this review is a summary of studies on the exploration of mechanisms underlying GLP-1 secretion. We not only summarize studies conducted over the past three decades on elucidating the role of nutritional components and hormonal factors in regulating GLP-1 secretion, but also present a few very recent studies showing the possible role of dietary polyphenols. Finally, the emerging role of gut microbiota in metabolic homeostasis with the potential implication on GLP-1 secretion is discussed.