This chapter discusses the role of metals, particularly iron (Fe) and copper (Cu), and non-redox metal zinc (Zn), in oxidative stress-related etiology of Alzheimer's disease (AD) and Parkinson's disease (PD). The authors highlight that both AD and PD are age-related disorders characterized by the deposition of abnormal proteins in the brain. In AD, the primary constituent of amyloid plaques is the amyloid-β protein (Aβ), while in PD, Lewy bodies consist of aggregates of α-synuclein. Both diseases are associated with increased oxidative stress, which can lead to neuronal death through direct modification of proteins by reactive oxygen species (ROS) or reactive nitrogen species (RNS) and indirect effects through lipid peroxidation products. The chapter details the biochemical changes in the brain of AD patients, including increased levels of Fe and Cu, enhanced protein and DNA oxidation, lipid peroxidation, and decreased levels of cytochrome c oxidase. These changes are linked to the formation of advanced glycation end products (AGEs), carbonyls, malondialdehyde (MDA), peroxynitrite, and heme oxygenase-1 (HO-1). In PD, oxidative stress is supported by increased levels in the substantia nigra pars compacta (SNc) and is associated with other factors such as inflammation, toxic action of nitric oxide (NO), protein clearance defects, and mitochondrial dysfunction. The authors also discuss the protective role of antioxidants, including glutathione (GSH), vitamin C, vitamin E, lipoic acid, flavonoids, and curcumin, in mitigating oxidative stress. They emphasize the importance of understanding the metal-induced formation of free radicals and the potential neuroprotective effects of antioxidants in preventing or slowing the progression of AD and PD. Additionally, an alternate hypothesis about the role of Aβ in AD is briefly discussed, suggesting that Aβ may be a secondary event rather than an initiating factor.This chapter discusses the role of metals, particularly iron (Fe) and copper (Cu), and non-redox metal zinc (Zn), in oxidative stress-related etiology of Alzheimer's disease (AD) and Parkinson's disease (PD). The authors highlight that both AD and PD are age-related disorders characterized by the deposition of abnormal proteins in the brain. In AD, the primary constituent of amyloid plaques is the amyloid-β protein (Aβ), while in PD, Lewy bodies consist of aggregates of α-synuclein. Both diseases are associated with increased oxidative stress, which can lead to neuronal death through direct modification of proteins by reactive oxygen species (ROS) or reactive nitrogen species (RNS) and indirect effects through lipid peroxidation products. The chapter details the biochemical changes in the brain of AD patients, including increased levels of Fe and Cu, enhanced protein and DNA oxidation, lipid peroxidation, and decreased levels of cytochrome c oxidase. These changes are linked to the formation of advanced glycation end products (AGEs), carbonyls, malondialdehyde (MDA), peroxynitrite, and heme oxygenase-1 (HO-1). In PD, oxidative stress is supported by increased levels in the substantia nigra pars compacta (SNc) and is associated with other factors such as inflammation, toxic action of nitric oxide (NO), protein clearance defects, and mitochondrial dysfunction. The authors also discuss the protective role of antioxidants, including glutathione (GSH), vitamin C, vitamin E, lipoic acid, flavonoids, and curcumin, in mitigating oxidative stress. They emphasize the importance of understanding the metal-induced formation of free radicals and the potential neuroprotective effects of antioxidants in preventing or slowing the progression of AD and PD. Additionally, an alternate hypothesis about the role of Aβ in AD is briefly discussed, suggesting that Aβ may be a secondary event rather than an initiating factor.