Atherosclerosis is a chronic inflammatory disease characterized by progressive vascular dysfunction and remains a leading cause of cardiovascular morbidity and mortality worldwide. Endothelial dysfunction is an early and critical event in atherogenesis, contributing to inflammation, leukocyte recruitment, plaque progression, and thrombotic complications. Increasing evidence indicates that vascular endothelial cells use bioelectrical signaling mechanisms to integrate mechanical, metabolic, and inflammatory cues and maintain vascular homeostasis. At the core of these regulatory networks are ion channels and transporters, which coordinate membrane potential, ionic fluxes, calcium homeostasis, redox balance, and downstream biochemical signaling to regulate endothelial function in vascular health and disease. Dysregulation of these pathways may promote oxidative stress, inflammation, endothelial senescence, apoptosis, endothelial-to-mesenchymal transition, and impaired vasodilatory function, thereby contributing to atherosclerotic progression. Understanding how ion channels regulate endothelial function may provide important insights into atherosclerosis and facilitate the development of novel therapeutic strategies aimed at restoring endothelial homeostasis and reducing cardiovascular risk.