Reactive oxygen species (ROS) are a group of highly reactive molecules containing oxygen. ROS are generated endogenously in different physiological processes such as metabolic system and wound healing responses. The biological responses of ROS are highly dependent on its concentration in the biological system. Natural polyphenols and catechol-containing compounds (i.e., mussel adhesive proteins, melanin, and polyphenols) demonstrate both pro- and antioxidant properties. These redox activities can be tailored to be used in various clinical applications. Here, we review the physiological generation and regulation of ROS and their effects in biological system and summarize the unique features of phenolic compounds and their incorporation into biomaterials for various biomedical applications.