Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and therefore become one of the most prominent global public health concerns. Puerarin, an isoflavone glycoside derived from Pueraria lobata (Willd.) Ohwi, has been identified as a pharmacologically active component with diverse benefits. A large number of experimental and clinical studies have demonstrated that puerarin is widely used in the treatment of CVDs, diabetes and its complications, Alzheimer’s disease, Parkinson’s disease, osteonecrosis, endometriosis and cancer. In this review, we systematically analyze the preclinical investigations of puerarin in CVDs, such as atherosclerosis, cardiac hypertrophy, heart failure, diabetic cardiovascular complications, myocardial infarction (MI), stroke and hypertension. In addition, the potential molecular targets of puerarin are also discussed. Furthermore,we summarize the clinical trails of puerarin in the treatment of CVDs. Finally, the therapeutic effects of puerarin derivatives and its drug delivery systems are overviewed.