This review explores the roles of oxidative stress (OS) and neuroinflammation in neurodegenerative diseases (NDDs), with a focus on amyotrophic lateral sclerosis (ALS). OS is defined as an imbalance between oxidants and antioxidants, often caused by reactive oxygen species (ROS), which can damage cellular components such as DNA, proteins, and lipids. Neuroinflammation, a key feature of NDDs, involves the activation of immune cells like microglia and astrocytes, leading to the release of pro-inflammatory cytokines and exacerbating neuronal damage. Both OS and neuroinflammation are interconnected, with OS contributing to neuroinflammation and vice versa. The review discusses the mechanisms by which OS and neuroinflammation contribute to the pathogenesis of NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and ALS. In ALS, OS and neuroinflammation are particularly significant, with evidence of increased ROS production, mitochondrial dysfunction, and neuroinflammatory responses. The review highlights the role of various genes, such as SOD1, TDP-43, and FUS, in the pathogenesis of ALS, and the impact of mutations in these genes on oxidative stress and neuroinflammation. The review also examines the therapeutic approaches targeting OS and neuroinflammation in NDDs, including the use of antioxidants, anti-inflammatory drugs, and mitochondrial-targeted therapies. Drugs such as Edaravone and Riluzole have shown some efficacy in reducing oxidative stress and neuroinflammation in ALS. Additionally, the review discusses the potential of repurposing existing drugs, such as Fingolimod, for the treatment of NDDs. Despite these efforts, the development of effective therapies remains challenging due to the complex pathophysiology of NDDs and the difficulty in translating findings from animal models to clinical practice. The review concludes that while OS and neuroinflammation are critical factors in NDDs, the exact mechanisms and their interplay remain areas of active research. Future studies are needed to better understand these processes and to develop more effective treatments for NDDs.This review explores the roles of oxidative stress (OS) and neuroinflammation in neurodegenerative diseases (NDDs), with a focus on amyotrophic lateral sclerosis (ALS). OS is defined as an imbalance between oxidants and antioxidants, often caused by reactive oxygen species (ROS), which can damage cellular components such as DNA, proteins, and lipids. Neuroinflammation, a key feature of NDDs, involves the activation of immune cells like microglia and astrocytes, leading to the release of pro-inflammatory cytokines and exacerbating neuronal damage. Both OS and neuroinflammation are interconnected, with OS contributing to neuroinflammation and vice versa. The review discusses the mechanisms by which OS and neuroinflammation contribute to the pathogenesis of NDDs, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and ALS. In ALS, OS and neuroinflammation are particularly significant, with evidence of increased ROS production, mitochondrial dysfunction, and neuroinflammatory responses. The review highlights the role of various genes, such as SOD1, TDP-43, and FUS, in the pathogenesis of ALS, and the impact of mutations in these genes on oxidative stress and neuroinflammation. The review also examines the therapeutic approaches targeting OS and neuroinflammation in NDDs, including the use of antioxidants, anti-inflammatory drugs, and mitochondrial-targeted therapies. Drugs such as Edaravone and Riluzole have shown some efficacy in reducing oxidative stress and neuroinflammation in ALS. Additionally, the review discusses the potential of repurposing existing drugs, such as Fingolimod, for the treatment of NDDs. Despite these efforts, the development of effective therapies remains challenging due to the complex pathophysiology of NDDs and the difficulty in translating findings from animal models to clinical practice. The review concludes that while OS and neuroinflammation are critical factors in NDDs, the exact mechanisms and their interplay remain areas of active research. Future studies are needed to better understand these processes and to develop more effective treatments for NDDs.