Krüppel-like factor 15 (KLF15) is a critical member of Krüppel-like factor (KLF) family containing zinc finger. Studies have shown that KLF15 plays an important role in regulating various signal transduction pathways and energy metabolism. KLF15 can play an anti-myocardial remodeling role by affecting myocyte enhancer factor 2 (MEF2), transforming growth factor β (TGF-β) and so on. In addition, KLF15 is the key factor to maintain ventricular arrhythmia and circadian rhythm. This paper reviews the physiological and pathological role of KLF15 in the heart and the latest research progress in cardiovascular diseases.