Cardiometabolic diseases (CMD) have a great burden in terms of morbidity and mortality worldwide. The vicious cycle of CMD consists of type II diabetes, hypertension, dyslipidemia, obesity, and atherosclerosis interacting and feedbacking each other. The natural flavonoid chrysin has been displayed to own a broad spectrum of therapeutic impacts for human health. Herein, we did an in-depth investigation of the novel mechanisms of chrysin's cardioprotection against cardiometabolic disorder. Studies have shown that chrysin protects the cardiovascular system by enhancing the intrinsic antioxidative defense system. This antioxidant boost by chrysin protects against several risk factors of cardiometabolic disorders including atherosclerosis, vascular inflammation and dysfunction, platelet aggregation, hypertension, dyslipidemia, cardiotoxicity, myocardial infarction, injury and remodeling, diabetes-induced injuries, and obesity. Chrysin also exhibited anti-inflammatory mechanisms through inhibiting pro-inflammatory pathways including NF-κB, MAPK, and PI3k/Akt. Furthermore, chrysin modulated NO pathway, RAS system, AGE/RAGE pathway, PPARs pathway which contributed to the risk factors of cardiometabolic disorders. Taken together, the mechanisms in which chrysin protects against cardiometabolic disorder are more than merely antioxidation and anti-inflammation in the cardiovascular system.