Glucagon-like peptide-1 (GLP-1) is a gut hormone that plays critical roles in linking ingestion, metabolic homeostasis, and cardiovascular function. Endogenous peripheral GLP-1 exerts its effects either in a paracrine or endocrine fashion, or via vagal sensory fibers and vagal motor fibers. The effects of endogenous central GLP-1 overlap in part with the effects of the peripheral hormone, but peripheral GLP-1 does not act by recruiting the central GLP-1 system. This review comprehensively examines the multifaceted roles of GLP-1 in regulating food intake, energy balance, and cardiac function, highlighting the therapeutic potential of GLP-1-based interventions for metabolic and cardiovascular diseases.