Superoxide dismutase (SOD) is a crucial antioxidant enzyme that plays a vital role in maintaining redox balance and detoxifying superoxide anions (O₂⁻) into molecular oxygen (O₂) and hydrogen peroxide (H₂O₂). SODs are expressed in neurons and glial cells throughout the central nervous system (CNS), both intracellularly and extracellularly. Endogenous oxidative stress (OS) linked with increased production of reactive oxygen metabolites (ROMs), inflammation, deregulation of redox balance, mitochondrial dysfunction, and bioenergetic crisis are key factors in neuronal loss in neurological diseases. Clinical and genetic studies have shown a direct correlation between mutations in the SOD gene and neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD), Parkinson’s Disease (PD), and Alzheimer’s Disease (AD). Therefore, inhibitors of OS are considered as a promising approach to prevent neuronal loss. SOD mimetics, such as Metalloporphyrin Mn (II)-cyclic polyamines, Nitroxides, and Mn (III)-Salen complexes, have been extensively used in the treatment of neurological disorders. SODs and SOD mimetics are promising future therapeutics in various diseases with OS-mediated pathology. The article reviews the classification, physiological role, and expression of SODs in the CNS, as well as their involvement in various neurological disorders, including Alzheimer’s, Parkinson’s, Huntington’s, ischemic stroke, depression, schizophrenia, and Down Syndrome.Superoxide dismutase (SOD) is a crucial antioxidant enzyme that plays a vital role in maintaining redox balance and detoxifying superoxide anions (O₂⁻) into molecular oxygen (O₂) and hydrogen peroxide (H₂O₂). SODs are expressed in neurons and glial cells throughout the central nervous system (CNS), both intracellularly and extracellularly. Endogenous oxidative stress (OS) linked with increased production of reactive oxygen metabolites (ROMs), inflammation, deregulation of redox balance, mitochondrial dysfunction, and bioenergetic crisis are key factors in neuronal loss in neurological diseases. Clinical and genetic studies have shown a direct correlation between mutations in the SOD gene and neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD), Parkinson’s Disease (PD), and Alzheimer’s Disease (AD). Therefore, inhibitors of OS are considered as a promising approach to prevent neuronal loss. SOD mimetics, such as Metalloporphyrin Mn (II)-cyclic polyamines, Nitroxides, and Mn (III)-Salen complexes, have been extensively used in the treatment of neurological disorders. SODs and SOD mimetics are promising future therapeutics in various diseases with OS-mediated pathology. The article reviews the classification, physiological role, and expression of SODs in the CNS, as well as their involvement in various neurological disorders, including Alzheimer’s, Parkinson’s, Huntington’s, ischemic stroke, depression, schizophrenia, and Down Syndrome.