This review explores the role of copper homeostasis and cuproptosis in atherosclerosis. Copper, an essential micronutrient, plays a crucial role in various physiological processes, but dysregulation of its homeostasis can lead to pathological alterations, including atherosclerosis. The concept of cuproptosis, a novel form of cell death induced by excess copper, has gained attention in recent years. The review provides an overview of cellular and systemic copper metabolism, linking copper dyshomeostasis to atherosclerosis through mechanisms such as oxidative stress, inflammation, endothelial dysfunction, and lipid metabolism. It also discusses the potential mechanisms of cuproptosis, its interactions with other forms of cell death, and the role of mitochondrial dysfunction in atherosclerosis. Finally, the review explores therapeutic strategies targeting cuproptosis, including copper chelators, copper ionophores, and modulating copper chaperone protein expression. The findings highlight the importance of understanding and managing copper homeostasis to prevent and treat atherosclerosis.This review explores the role of copper homeostasis and cuproptosis in atherosclerosis. Copper, an essential micronutrient, plays a crucial role in various physiological processes, but dysregulation of its homeostasis can lead to pathological alterations, including atherosclerosis. The concept of cuproptosis, a novel form of cell death induced by excess copper, has gained attention in recent years. The review provides an overview of cellular and systemic copper metabolism, linking copper dyshomeostasis to atherosclerosis through mechanisms such as oxidative stress, inflammation, endothelial dysfunction, and lipid metabolism. It also discusses the potential mechanisms of cuproptosis, its interactions with other forms of cell death, and the role of mitochondrial dysfunction in atherosclerosis. Finally, the review explores therapeutic strategies targeting cuproptosis, including copper chelators, copper ionophores, and modulating copper chaperone protein expression. The findings highlight the importance of understanding and managing copper homeostasis to prevent and treat atherosclerosis.