Oxidative stress is a fundamental pathophysiological process resulting from the imbalance between the overproduction of reactive oxygen species (ROS/RNS) and antioxidant defense systems, leading to damage in proteins, lipids, and nucleic acids. This condition plays a central role in the development of numerous chronic diseases such as cancer, cardiovascular diseases, neurodegenerative disorders, diabetes, and aging. While endogenous and exogenous antioxidants are important in limiting oxidative stress, conventional antioxidant applications have significant limitations, including low bioavailability, rapid metabolism, lack of tissue-specific targeting, and dose-dependent pro-oxidant effects. This book chapter comprehensively addresses the innovative approaches that nanotechnology brings to antioxidant strategies. The chapter discusses in detail how nanocarrier systems enhance bioavailability by protecting antioxidant molecules from enzymatic and chemical degradation, providing controlled and targeted release, and optimizing therapeutic efficacy. Furthermore, the ability of metal oxide nanoparticles such as cerium oxide, manganese oxide, and platinum to exhibit intrinsic antioxidant effects through their enzyme-mimetic (nanozyme) activities demonstrates that nanotechnology can be used not only as a carrier but also as an active therapeutic agent. In this chapter, major nanocarrier platforms such as liposomes, nanoemulsions, dendrimers, polymeric nanoparticles, and metal oxide nanostructures are comparatively examined in terms of their advantages, limitations, and clinical potential. In addition, enhancing bioavailability, passive and active targeting mechanisms, stimulus-responsive release systems, and clinical/preclinical application examples are evaluated. In conclusion, nanotechnology-based antioxidant approaches offer strong potential for developing more effective, safe, and targeted therapeutic strategies in the treatment of diseases associated with oxidative stress.