Abstract: Krüppel-like factor 2 (KLF2) is a zinc finger transcription factor that regulates the transcription process of the target genes either positively or negatively by binding to the cis-acting elements of these genes. Studies have shown that KLF2 is highly expressed in endothelial cells, and participates in the regulation of various signaling pathways involved in various biological processes, including cell differentiation, inflammatory response, and oxidative stress, thereby alleviating vascular endothelial dysfunction and exerting a beneficial anti-atherosclerotic effect. This article summarizes the anti-atherosclerotic functions and mechanisms of KLF2, and introduces recent advances in research on drugs regulating KLF2-related signaling pathways, aiming to provide new strategies for the development of antiatherosclerotic drugs.