Kruppel-like factor 15 (KLF15) is a subtype of the Kruppellike family of transcription factors (KLFs). KLFs have three high-fidelity zinc fingers at the carboxyl terminus that enable them to regulate the biological processes of proliferation, differentiation, cellular development, and apoptosis. KLF15 is highly expressed in the kidney, pancreas, and cardiac and skeletal muscle, and plays an essential role in the development and occurrence of multiple system diseases. In this paper, we underscored the important relationship between KLF15 and cardiovascular diseases such as atherosclerosis, heart failure, arrhythmia, aortic lesions, etc. On this basis, we identified KLF15 as a potential therapeutic target for the treatment of cardiovascular disease.