Antioxidant potential of plants is crucial for combating oxidative stress, a key factor in many diseases. Plants naturally produce non-enzymatic antioxidants like ascorbic acid and glutathione, which help neutralize reactive oxygen species (ROS). In vitro assays show potent antioxidant activity in many plants, but their in vivo efficacy is not always confirmed. This review discusses the physiological and redox biology of plants and humans to better understand plant antioxidants as therapeutic agents. It highlights the limitations of in vitro assays and the need for in vivo studies to validate therapeutic applications. Plants have efficient antioxidant defense systems, including enzymatic and non-enzymatic components, which help manage ROS. However, their antioxidant activity can be influenced by environmental stress and physiological processes. Secondary metabolites like phenolics, flavonoids, and tannins play significant roles in antioxidant activity. While in vitro methods are useful for screening, they often fail to predict in vivo effectiveness due to factors like absorption, metabolism, and interactions with other compounds. The review emphasizes the importance of combining in vitro and in vivo studies to accurately assess the therapeutic potential of plant antioxidants. It also discusses the role of antioxidants in human health, noting that while plants have evolved efficient antioxidant systems, humans rely more on dietary antioxidants. The review concludes that a comprehensive approach combining both in vitro and in vivo studies is necessary to fully understand and utilize the therapeutic potential of plant antioxidants.Antioxidant potential of plants is crucial for combating oxidative stress, a key factor in many diseases. Plants naturally produce non-enzymatic antioxidants like ascorbic acid and glutathione, which help neutralize reactive oxygen species (ROS). In vitro assays show potent antioxidant activity in many plants, but their in vivo efficacy is not always confirmed. This review discusses the physiological and redox biology of plants and humans to better understand plant antioxidants as therapeutic agents. It highlights the limitations of in vitro assays and the need for in vivo studies to validate therapeutic applications. Plants have efficient antioxidant defense systems, including enzymatic and non-enzymatic components, which help manage ROS. However, their antioxidant activity can be influenced by environmental stress and physiological processes. Secondary metabolites like phenolics, flavonoids, and tannins play significant roles in antioxidant activity. While in vitro methods are useful for screening, they often fail to predict in vivo effectiveness due to factors like absorption, metabolism, and interactions with other compounds. The review emphasizes the importance of combining in vitro and in vivo studies to accurately assess the therapeutic potential of plant antioxidants. It also discusses the role of antioxidants in human health, noting that while plants have evolved efficient antioxidant systems, humans rely more on dietary antioxidants. The review concludes that a comprehensive approach combining both in vitro and in vivo studies is necessary to fully understand and utilize the therapeutic potential of plant antioxidants.