Epidemiological studies strongly imply the important benefits of dietary consumption of polyphenols in human health. As plant-based nutraceuticals, polyphenols express roles in preventing diseases, particularly associated with a high ability to decrease the risk of diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. Magnolol and honokiol are two important components of Magnolia bark extract isomers of polyphenolic compounds with the scientific name Magnolia officinalis and exhibit anti-oxidative, anti-inflammatory, and other types of actions in cells with interaction in various cellular signaling pathways. Today, these types of nutraceuticals are used worldwide as food supplements due to their multiple action mechanisms in protecting organs, not only under pathological conditions but also during physiological aging. Among the important benefits of Magnolia bark extract are control of blood pressure, reduction of ventricular arrhythmia, protection against myocardial infarction and ischemia/reperfusion injury, and prevention of atherosclerosis. All these protective actions generally include the inhibition of neutrophil infiltration and apoptosis in the myocardium, the prevention of increases in proliferation in vascular smooth muscle cells, and endothelial cell death. They also inhibit acute inflammation, and macrophage activation, as well as aggregation, activation, and migration of neutrophils in the myocardium and vessels. Since these actions depend on their doses and cell types, it is important to consider their cell-type specificity and dose-related effects before using a therapeutic agent. In the present chapter, we aimed to document the benefits of Magnolia bark extract, including magnolol, honokiol, or both, focusing on cardiovascular protection, and pointing out their great potential for lowering high risks and, thereby, preventing heart diseases.