The excessive production of reactive oxygen species (ROS) can lead to oxidative stress, which has significant biological consequences, including oxidative damage to biomolecules, disruption of signal transduction, mutation, and cell apoptosis. Oxidative stress is implicated in various chronic inflammatory diseases such as cardiovascular diseases, diabetes, cancer, and neurodegenerative processes. While many antioxidant trials have shown no effect or even harmful effects, targeting oxidative stress remains a promising therapeutic approach. This review explores several natural and synthetic antioxidants as potential therapeutic options for chronic inflammatory diseases. Key enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase play crucial roles in maintaining redox homeostasis and are potential targets for designing catalytic drugs. Natural antioxidants, such as vitamins C and E, carotenoids, and polyphenols, have demonstrated beneficial effects in various chronic inflammatory conditions. Synthetic antioxidants, including SOD mimetics, are also under investigation for their therapeutic potential. However, further safety assessments are necessary to ensure their effectiveness and safety in clinical settings.The excessive production of reactive oxygen species (ROS) can lead to oxidative stress, which has significant biological consequences, including oxidative damage to biomolecules, disruption of signal transduction, mutation, and cell apoptosis. Oxidative stress is implicated in various chronic inflammatory diseases such as cardiovascular diseases, diabetes, cancer, and neurodegenerative processes. While many antioxidant trials have shown no effect or even harmful effects, targeting oxidative stress remains a promising therapeutic approach. This review explores several natural and synthetic antioxidants as potential therapeutic options for chronic inflammatory diseases. Key enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase play crucial roles in maintaining redox homeostasis and are potential targets for designing catalytic drugs. Natural antioxidants, such as vitamins C and E, carotenoids, and polyphenols, have demonstrated beneficial effects in various chronic inflammatory conditions. Synthetic antioxidants, including SOD mimetics, are also under investigation for their therapeutic potential. However, further safety assessments are necessary to ensure their effectiveness and safety in clinical settings.