Cardiovascular disease (CVD) remains a leading cause of mortality worldwide. In recent years, bioactive small molecules (BSMs) have been demonstrated to play crucial roles in regulating different pathological process of cardiovascular diseases, which provides potential clinical applications. Here, we summarized five main chrematistics of bioactive small molecules in the field of cardiovascular to depict a whole regulation network of these small molecules and discuss the potential clinical therapies of bioactive small molecules including drug development and biomarkers in cardiovascular diseases.