This review critically examines the experimental use of melatonin to prevent coronary artery pathologies, focusing on its anti-atherosclerotic actions. Melatonin reduces LDL oxidation and triglyceride levels, lowers endothelial malfunction, limits adhesion molecule formation, prevents macrophage polarization to the M1 pro-inflammatory phenotype, changes cellular metabolism, scavenges destructive reactive oxygen species (ROS), prevents the proliferation and invasion of arterial smooth muscle cells, restricts the ingrowth of blood vessels from the vasa vasorum, and stabilizes the plaque cap to reduce the risk of rupture. Additionally, melatonin inhibits diabetic hyperglycemia, which exacerbates atherosclerotic plaque formation. The review highlights the potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans, emphasizing the need for clinical trials to further explore its therapeutic benefits.This review critically examines the experimental use of melatonin to prevent coronary artery pathologies, focusing on its anti-atherosclerotic actions. Melatonin reduces LDL oxidation and triglyceride levels, lowers endothelial malfunction, limits adhesion molecule formation, prevents macrophage polarization to the M1 pro-inflammatory phenotype, changes cellular metabolism, scavenges destructive reactive oxygen species (ROS), prevents the proliferation and invasion of arterial smooth muscle cells, restricts the ingrowth of blood vessels from the vasa vasorum, and stabilizes the plaque cap to reduce the risk of rupture. Additionally, melatonin inhibits diabetic hyperglycemia, which exacerbates atherosclerotic plaque formation. The review highlights the potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans, emphasizing the need for clinical trials to further explore its therapeutic benefits.