The article reviews the significance of plant antioxidants and their therapeutic applications. Plants have innate abilities to synthesize non-enzymatic antioxidants, such as ascorbic acid and glutathione, which can mitigate oxidative damage caused by reactive oxygen species (ROS). While in vitro assays often reveal potent antioxidant activity in plants, the in vivo therapeutic efficacy of these antioxidants is less clear due to the need for physiopharmacological processes such as absorption, distribution, metabolism, storage, and excretion. The authors highlight the importance of understanding the physiology and redox biology of both plants and humans to improve the interpretation of in vitro and in vivo antioxidant potential assessment studies. They also discuss the limitations of antioxidant activity measurement assays and propose a combined in vitro and in vivo strategy to attribute more precise therapeutic values to plant antioxidants. The article emphasizes the need for comprehensive studies to bridge the gap between in vitro and in vivo findings, ensuring the safe and effective use of plant antioxidants in therapeutic applications.The article reviews the significance of plant antioxidants and their therapeutic applications. Plants have innate abilities to synthesize non-enzymatic antioxidants, such as ascorbic acid and glutathione, which can mitigate oxidative damage caused by reactive oxygen species (ROS). While in vitro assays often reveal potent antioxidant activity in plants, the in vivo therapeutic efficacy of these antioxidants is less clear due to the need for physiopharmacological processes such as absorption, distribution, metabolism, storage, and excretion. The authors highlight the importance of understanding the physiology and redox biology of both plants and humans to improve the interpretation of in vitro and in vivo antioxidant potential assessment studies. They also discuss the limitations of antioxidant activity measurement assays and propose a combined in vitro and in vivo strategy to attribute more precise therapeutic values to plant antioxidants. The article emphasizes the need for comprehensive studies to bridge the gap between in vitro and in vivo findings, ensuring the safe and effective use of plant antioxidants in therapeutic applications.