This review discusses the beneficial effects of melatonin in protecting against heart failure. Melatonin, an endogenous molecule, has been shown to reduce the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. Experimental studies indicate that melatonin has anti-atherosclerotic actions, including reducing LDL oxidation, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging reactive oxygen species (ROS), preventing the proliferation and invasion of arterial smooth muscle cells, restricting blood vessel ingrowth from the vasa vasorum, and stabilizing the atherosclerotic plaque. Melatonin also inhibits diabetic hyperglycemia, which aggravates atherosclerotic plaque formation. The potential value of melatonin as a non-toxic inhibitor of cardiac pathology in humans should be seriously considered through clinical trials. Atherosclerosis involves endothelial dysfunction, subendothelial lipid accumulation, foam cell formation, and vascular smooth muscle cell proliferation. The formation of atherosclerotic plaques contributes to the narrowing of coronary arteries, leading to angina and potentially a heart attack. The progression of atherosclerosis is influenced by factors such as hypertension, smoking, and sustained hyperglycemia. The development of atherosclerotic plaques is associated with inflammation, fibrosis, and the formation of a necrotic core. The stability of the plaque is crucial in preventing rupture, which can lead to a heart attack or stroke. Melatonin has multiple actions that resist atheroma formation and malfunction. It lowers triglycerides and reduces oxidized LDL cholesterol, inhibits the development of adhesion molecules, impedes the polarization of macrophages to the pro-inflammatory M1 phenotype, scavenges ROS, inhibits the proliferation and migration of vascular smooth muscle cells, has anti-angiogenic properties, and stabilizes the atherosclerotic cap. These actions contribute to the prevention of plaque rupture and the progression of atherosclerosis. Melatonin also plays a role in maintaining mitochondrial redox homeostasis and ensuring unaltered oxidative phosphorylation and ATP production. It influences the metabolism of cells in the plaque, including the conversion of pyruvate to lactate and the regulation of the citric acid cycle. Melatonin's ability to neutralize ROS and stimulate antioxidative enzymes helps reduce endothelial damage and delay the onset of atheroma. Melatonin has anti-inflammatory and anti-fibrotic actions in the heart, reducing cardiac fibrosis and improving cardiac function. It also has protective effects against hypertensive heart disease, reducing collagen content and improving mitochondrial function. In diabetic cardiomyopathy, melatonin reduces cardiac fibrosis, preserves cardiomyocyte viability, and improves mitochondrial function. Melatonin's ability to reduce oxidative stress and inflammation is crucial in preventing the progression of heart failure. Melatonin's protective actions againstThis review discusses the beneficial effects of melatonin in protecting against heart failure. Melatonin, an endogenous molecule, has been shown to reduce the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. Experimental studies indicate that melatonin has anti-atherosclerotic actions, including reducing LDL oxidation, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging reactive oxygen species (ROS), preventing the proliferation and invasion of arterial smooth muscle cells, restricting blood vessel ingrowth from the vasa vasorum, and stabilizing the atherosclerotic plaque. Melatonin also inhibits diabetic hyperglycemia, which aggravates atherosclerotic plaque formation. The potential value of melatonin as a non-toxic inhibitor of cardiac pathology in humans should be seriously considered through clinical trials. Atherosclerosis involves endothelial dysfunction, subendothelial lipid accumulation, foam cell formation, and vascular smooth muscle cell proliferation. The formation of atherosclerotic plaques contributes to the narrowing of coronary arteries, leading to angina and potentially a heart attack. The progression of atherosclerosis is influenced by factors such as hypertension, smoking, and sustained hyperglycemia. The development of atherosclerotic plaques is associated with inflammation, fibrosis, and the formation of a necrotic core. The stability of the plaque is crucial in preventing rupture, which can lead to a heart attack or stroke. Melatonin has multiple actions that resist atheroma formation and malfunction. It lowers triglycerides and reduces oxidized LDL cholesterol, inhibits the development of adhesion molecules, impedes the polarization of macrophages to the pro-inflammatory M1 phenotype, scavenges ROS, inhibits the proliferation and migration of vascular smooth muscle cells, has anti-angiogenic properties, and stabilizes the atherosclerotic cap. These actions contribute to the prevention of plaque rupture and the progression of atherosclerosis. Melatonin also plays a role in maintaining mitochondrial redox homeostasis and ensuring unaltered oxidative phosphorylation and ATP production. It influences the metabolism of cells in the plaque, including the conversion of pyruvate to lactate and the regulation of the citric acid cycle. Melatonin's ability to neutralize ROS and stimulate antioxidative enzymes helps reduce endothelial damage and delay the onset of atheroma. Melatonin has anti-inflammatory and anti-fibrotic actions in the heart, reducing cardiac fibrosis and improving cardiac function. It also has protective effects against hypertensive heart disease, reducing collagen content and improving mitochondrial function. In diabetic cardiomyopathy, melatonin reduces cardiac fibrosis, preserves cardiomyocyte viability, and improves mitochondrial function. Melatonin's ability to reduce oxidative stress and inflammation is crucial in preventing the progression of heart failure. Melatonin's protective actions against