Atherosclerosis, the underlying pathophysiological basis of cardiovascular disease, has been recognized as a lipid-driven chronic inflammatory disease. Sterol carrier protein 2 (SCP-2) is a 13-kDa non-specific lipid-transfer protein expressed by various tissues and cells, such as liver, heart, vascular smooth muscle cells (VSMCs), and macrophages. SCP-2 has an extensive role in cardiovascular and metabolic diseases. Recently, SCP-2 was reported to promote the development of atherosclerosis by regulating lipid metabolism and peroxidation, endocannabinoid metabolism, vascular inflammation, and fatty acid metabolism. In this review, we summarized the recent advances regarding the role of SCP-2 in the pathogenesis of atherosclerosis and tried to provide a rationale for future investigation and a better understanding of the biological functions of SCP-2 in atherosclerotic cardiovascular disease.