The novel role of oxidants and antioxidants as part of cell signaling cascades has opened new areas of research in several disease states and their therapeutic strategies. For successful therapeutic manipulation of reactive oxygen species (ROS)-mediated cellular signaling pathways, it would necessitate control of the critical balance of oxidants/antioxidants in the target site by the antioxidant. Another way of controlling the critical balance is to avoid excessive generation of ROS from nutrients and/or drugs. From the viewpoint of controlling the balance between the oxidant and antioxidant status, this review focuses on the prodrug approach for delivery systems of vitamin E, a major antioxidant nutrient in the membrane, and on the reductive activation-independent delivery system of vitamin K hydroquinone by a prodrug approach, which can avoid excessive generation of ROS synchronized with the activation process of vitamin K.