Oxidative stress caused by reactive oxygen species (ROS) occurs as events in which living tissues contact certain materials. These events include cell cultures and implantation of materials. Because of the high reactivity of ROS, they damage cells by oxidizing DNA, lipids, and proteins. Conversely, ROS also act as signaling molecules regulating cellular morphology. In particular, mitochondrial ROS are involved in the regulation of cellular physiology, including differentiation, autophagy, metabolic adaptation, apoptosis, and immunity. The balance between generation and elimination of ROS is essential for signaling pathways and proper cell function, and redox imbalance leads to cellular dysfunction and disturbs cellular homeostasis. To reduce oxidative stress, versatile antioxidants, including natural compounds, have been used; however, their poor bioavailability and pro-oxidant effects have limited the versatility of these antioxidants. Recent developments of antioxidative biointerfaces may represent a potent solution to this issue. Designed biointerfaces composed of polymer antioxidants eliminate excessive ROS at the interface between living tissues and materials, and do not disturb regulated redox balance inside cells, thus eliminating unexpected cell responses, such as inflammation and dysfunction.