Oxidative stress plays a crucial role in cellular physiology, influencing both normal biological processes and disease pathogenesis (Afrose et al., 2025; Gorrini et al., 2013; Hybertson et al., 2011; Jiao et al., 2024; Kimball et al., 2021; Sies et al., 2024; van der Pol et al., 2019). It arises from an imbalance between reactive oxygen species (ROS) and the body's ability to detoxify these reactive intermediates using antioxidant systems (Brieger et al., 2012). While ROS serves essential signaling functions at physiological levels, excessive accumulation leads to oxidative damage, impacting lipids, proteins, and DNA. This damage has been implicated in various chronic diseases, including cardiovascular diseases, neurodegenerative disorders, and cancer.

To counteract oxidative stress, biological systems have evolved intricate antioxidant defense mechanisms. Antioxidants are molecules that neutralize ROS, preventing cellular damage. They are broadly classified into enzymatic antioxidants, such as superoxide dismutase (SOD), catalases (CAT), glutathione peroxidases (GPx), and peroxiredoxins (Prx), and non-enzymatic antioxidants, including vitamins (e.g., vitamin A, C, and E), glutathione (GSH), and coenzyme Q10 (CoQ10) (Gulcin, 2025a). The study of antioxidants has a long and rich history, marked by significant discoveries that have shaped our understanding of redox biology and therapeutic strategies for oxidative stress-related diseases. Fig. 1 provides a historical timeline of key milestones in antioxidant research, showcasing landmark discoveries such as the identification of CAT in 1900, the discovery of key antioxidant vitamins (A, C, and E), and the characterization of essential antioxidant enzymes like SOD, GPx, and Prx. These milestones have provided fundamental insights into the mechanisms of oxidative stress and antioxidant defense, paving the way for current and future research (Fig. 1).

While many insights into the biological effects of antioxidants have been derived from in vitro and animal studies, translation to human health requires evidence from well-designed clinical trials. To address this, we discuss key clinical trial findings in a later section of this review, providing an integrated perspective from basic research to clinical applications.