Oxidative stress plays a crucial part in the progression of numerous neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Sclerosis, and Huntington’s disease. This chapter delves into the mechanisms of oxidative stress and its significant impact on these disorders, providing a comprehensive overview of current research and therapeutic strategies. It starts with exploring the sources of reactive oxygen species (ROS) that contribute to oxidative stress, along with the body’s major antioxidant defense systems, considering the mechanisms of oxidative injury, encompassing lipid peroxidation, DNA damage, and protein oxidation. The discussion then continues to the role of oxidative stress in Alzheimer’s disease, focusing on how it promotes amyloid-beta production, tau phosphorylation, and mitochondrial dysfunction, all of which contribute to neurodegeneration. Similarly, in Parkinson’s disease, oxidative stress plays a major role in the degeneration of dopaminergic neurons and mitochondrial impairments. Huntington’s disease is characterized by oxidative damage due to the toxic effects of the mutant huntingtin protein and mitochondrial abnormalities. In multiple sclerosis, oxidative stress leads to demyelination and neuroinflammation, exacerbating the disease’s progression. Subsequently, the chapter addresses the common and exceptional oxidative stress mechanisms across these neurodegenerative diseases, propounding a comparative analysis. Therapeutic strategies targeting oxidative stress are discussed in detail for each disease and those that target the shared pathways, including antioxidant therapies, lifestyle modifications such as diet and exercise, and emerging treatments. Overall, this chapter seeks to elucidate the complex interplay between oxidative stress and neurodegeneration, facilitating the development of more efficacious treatments and better patient outcomes.