The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), a G protein-coupled receptor, is found on various cell types in the human body and plays a key role in regulating blood glucose, lipid metabolism, and other biological functions. GLP-1R agonists (GLP-1RAs) have become a focal point in medical research due to their innovative mechanisms, therapeutic efficacy, and broad applications. This review article discusses the development of GLP-1 drugs, from their initial discovery to clinical application, and explores their potential in treating various diseases, including obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, and cancers. It also highlights the pharmacological mechanisms, signaling pathways, and clinical trial data of GLP-1RAs, emphasizing their extensive therapeutic benefits. The article also covers the history and milestones of GLP-1 research, including the discovery of GLP-1, the development of exendin-4, and the approval of exenatide as the first GLP-1 analog. It discusses the development of various GLP-1RAs, such as exenatide, liraglutide, albiglutide, dulaglutide, semaglutide, and beinaglutide, and their mechanisms of action, including weight loss, blood glucose control, and cardiovascular benefits. The article also explores the development of dual and triple agonists, which target multiple receptors to enhance therapeutic effects. Additionally, it discusses the potential of small molecule GLP-1RAs and their advantages over traditional protein-based drugs. The review concludes with an overview of the classical pathophysiological mechanisms of GLP-1, including its signaling pathways, interactions with other pathways, and its role in metabolic diseases such as T2DM and obesity. The article emphasizes the significant potential of GLP-1RAs in the medical field and their promising future in treating a wide range of diseases.The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), a G protein-coupled receptor, is found on various cell types in the human body and plays a key role in regulating blood glucose, lipid metabolism, and other biological functions. GLP-1R agonists (GLP-1RAs) have become a focal point in medical research due to their innovative mechanisms, therapeutic efficacy, and broad applications. This review article discusses the development of GLP-1 drugs, from their initial discovery to clinical application, and explores their potential in treating various diseases, including obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, and cancers. It also highlights the pharmacological mechanisms, signaling pathways, and clinical trial data of GLP-1RAs, emphasizing their extensive therapeutic benefits. The article also covers the history and milestones of GLP-1 research, including the discovery of GLP-1, the development of exendin-4, and the approval of exenatide as the first GLP-1 analog. It discusses the development of various GLP-1RAs, such as exenatide, liraglutide, albiglutide, dulaglutide, semaglutide, and beinaglutide, and their mechanisms of action, including weight loss, blood glucose control, and cardiovascular benefits. The article also explores the development of dual and triple agonists, which target multiple receptors to enhance therapeutic effects. Additionally, it discusses the potential of small molecule GLP-1RAs and their advantages over traditional protein-based drugs. The review concludes with an overview of the classical pathophysiological mechanisms of GLP-1, including its signaling pathways, interactions with other pathways, and its role in metabolic diseases such as T2DM and obesity. The article emphasizes the significant potential of GLP-1RAs in the medical field and their promising future in treating a wide range of diseases.