This review discusses the antioxidant mechanisms of polyphenol compounds related to iron binding. Polyphenols are widely studied for their antioxidant properties, and their activity is often attributed to their ability to prevent damage from reactive oxygen species (ROS) or to prevent the generation of these species by binding iron. The primary focus of this review is on the interaction between polyphenols and iron as a mechanism of antioxidant activity. Polyphenols typically contain a three-membered flavan ring system, and they are found in various foods such as green and black teas, coffee, fruits, vegetables, olive oil, red and white wines, and chocolate. They are present in medium to high milligram quantities per serving. Polyphenols have various biological activities, including antioxidant, anti-inflammatory, antibacterial, and antiviral effects. They also have cardiovascular effects, such as vasodilation, and can bind many different proteins, inhibit enzymes, and prevent neurodegenerative diseases and cancer. They can induce apoptosis in cancer cells, suggesting a role in cancer senescence. Oxidative stress, caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS), damages proteins, lipids, and DNA. The Fenton reaction is a key process in ROS generation, and iron plays a pivotal role in this reaction. Polyphenols can bind iron and prevent the formation of ROS, thereby reducing oxidative stress. The stability constants of iron-polyphenol complexes are important in understanding their antioxidant activity. Catecholate, gallate, and semiquinone ligands are effective metal chelators and can bind iron. The stability constants for iron-polyphenol complexes provide insight into their antioxidant behavior. Polyphenols can reduce iron to Fe²⁺, which can then participate in the Fenton reaction and generate ROS. This process is often referred to as autooxidation. Polyphenols can also protect against DNA damage by preventing the formation of ROS and by chelating iron. The protective effects of polyphenols in blood and plasma are also discussed, as well as their role in preventing neurodegenerative diseases. The review also covers various assays used to quantify the inhibition of iron-mediated DNA damage by polyphenols, such as DNA gel electrophoresis and the deoxyribose assay. The review concludes that polyphenols have a wide range of biological activities, and their ability to bind iron is a key factor in their antioxidant activity. Further research is needed to confirm the role of iron binding in the antioxidant activity of polyphenols in animal models and to test their potential in clinical trials for the prevention and treatment of diseases related to iron-mediated DNA damage and other oxidative damage.This review discusses the antioxidant mechanisms of polyphenol compounds related to iron binding. Polyphenols are widely studied for their antioxidant properties, and their activity is often attributed to their ability to prevent damage from reactive oxygen species (ROS) or to prevent the generation of these species by binding iron. The primary focus of this review is on the interaction between polyphenols and iron as a mechanism of antioxidant activity. Polyphenols typically contain a three-membered flavan ring system, and they are found in various foods such as green and black teas, coffee, fruits, vegetables, olive oil, red and white wines, and chocolate. They are present in medium to high milligram quantities per serving. Polyphenols have various biological activities, including antioxidant, anti-inflammatory, antibacterial, and antiviral effects. They also have cardiovascular effects, such as vasodilation, and can bind many different proteins, inhibit enzymes, and prevent neurodegenerative diseases and cancer. They can induce apoptosis in cancer cells, suggesting a role in cancer senescence. Oxidative stress, caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS), damages proteins, lipids, and DNA. The Fenton reaction is a key process in ROS generation, and iron plays a pivotal role in this reaction. Polyphenols can bind iron and prevent the formation of ROS, thereby reducing oxidative stress. The stability constants of iron-polyphenol complexes are important in understanding their antioxidant activity. Catecholate, gallate, and semiquinone ligands are effective metal chelators and can bind iron. The stability constants for iron-polyphenol complexes provide insight into their antioxidant behavior. Polyphenols can reduce iron to Fe²⁺, which can then participate in the Fenton reaction and generate ROS. This process is often referred to as autooxidation. Polyphenols can also protect against DNA damage by preventing the formation of ROS and by chelating iron. The protective effects of polyphenols in blood and plasma are also discussed, as well as their role in preventing neurodegenerative diseases. The review also covers various assays used to quantify the inhibition of iron-mediated DNA damage by polyphenols, such as DNA gel electrophoresis and the deoxyribose assay. The review concludes that polyphenols have a wide range of biological activities, and their ability to bind iron is a key factor in their antioxidant activity. Further research is needed to confirm the role of iron binding in the antioxidant activity of polyphenols in animal models and to test their potential in clinical trials for the prevention and treatment of diseases related to iron-mediated DNA damage and other oxidative damage.