Background: Cardiovascular diseases (CVD) remain the primary cause of global mortality, necessitating innovative therapeutic approaches beyond traditional neurohormonal blockade and lipid-lowering therapies. Recent advancements have highlighted the gut microbiota as a dynamic endocrine organ that communicates with the host cardiovascular system via small molecule metabolites. While deleterious metabolites like trimethylamine N-oxide (TMAO) are well-characterized, a distinct panel of commensal-derived cardioprotective metabolites has emerged, presenting new avenues for drug discovery. Objective:This narrative review synthesizes current evidence (2020-2026) regarding the cardioprotective metabolome, exploring the mechanisms by which gut microbial derivatives mitigate atherosclerosis, heart failure, myocardial ischemia reperfusion injury, and metabolic syndrome, while highlighting their transition from preclinical discoveries to clinical therapeutics