Schisandra chinensis fruit extract (SCE) has traditionally been used as an oriental medicine for the treatment of various human diseases, including cardiovascular disease. Advances in scientific knowledge and analytical technologies provide opportunities for translational research involving S. chinensis; such research may contribute to future drug discovery. To date, emerging experimental evidence supports the therapeutic effects of the SCE or its bioactive lignan ingredients in cardiovascular disease, unraveling the mechanistic basis for their pharmacological actions. In the present review, we highlight SCE and its lignans as promising resources for the development of safe, effective, and multi-targeted agents against cardiovascular disease. Moreover, we offer novel insight into future challenges and perspective on S. chinensis research to future clinical investigations and healthcare strategies.