Nanoparticle-mediated gene therapy shows great promise for treating neurological disorders by delivering therapeutic genes to specific brain cell types, enhancing efficacy, and minimizing off-target effects. This approach leverages the unique properties of nanoparticles to address challenges faced by traditional delivery methods, such as viral vectors and naked DNA/RNA. Neurological disorders, including Alzheimer’s, Parkinson’s, Huntington’s disease, spinal muscular atrophy, and ALS, often lack effective treatments beyond symptom relief. Nanoparticles offer several advantages: they protect therapeutic genes from degradation, improving stability and bioavailability for targeted delivery to the brain. Surface modifications with ligands or antibodies enable precise targeting to neurons, glial cells, or other relevant brain cells, reducing exposure to nontarget tissues. Nanoparticles can cross the blood-brain barrier (BBB) via strategies like receptor-mediated transcytosis or BBB disruption, ensuring therapeutic genes reach the brain parenchyma. Additionally, they can incorporate stimuli-responsive release mechanisms for controlled, spatiotemporal gene delivery, enhancing precision and minimizing systemic toxicity. Various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles, are being explored for their stability, biocompatibility, and customizable properties. Preclinical studies have shown promising results in animal models, improving symptoms and neuronal survival, paving the way for clinical trials in neurodegenerative diseases. However, challenges remain, such as optimizing BBB penetration, reducing immunogenicity and toxicity, and ensuring long-term stability and gene expression. This book chapter discusses the potential of nanoparticle-mediated gene therapy to revolutionize neurological disorder treatments, emphasizing the need for ongoing research to overcome technical hurdles and advance clinical development.