Novel therapeutic strategies using nucleic acid drugs, such as plasmid DNA (pDNA) and nuclear factor-κB (NFκB) decoy, have been sought for non-treatable neurological disorders. Among them, the application of pDNA has been extensively studied in diabetic neuropathy. Since growth factors, such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), have both neurotrophic and angiogenic properties, intramuscular injection of pDNA encoding these genes has been examined and shown to be effective for treatment in experimental animals and also in clinical trials. These growth factors have also been shown to accelerate neuroprotection, angiogenesis, and regeneration in the brain, and overexpression of these factors showed therapeutic effects in cerebral ischemia in rodents. Inhibition of inflammation is another strategy to treat cerebrovascular diseases. Recent studies suggest that NFκB plays critical roles in the formation of cerebral aneurysms, and inhibition of its function by NFκB decoy was shown to prevent cerebral aneurysm enlargement through inhibition of NFκB-mediated inflammation. In the field of neurodegenerative disease, the potential of pDNA as a tool for vaccination has attracted researchers since pDNA itself has shown adjuvant properties and the potential to induce immunity or immune tolerance. pDNA encoding disease antigens, such as amyloid-Aβ in Alzheimer disease or myelin basic protein in multiple sclerosis (MS), was shown to have therapeutic effects in rodents, and its efficacy and safety were reported in a phase I/II clinical study in MS. In this review, we discuss the potential and problems of nucleic acid drugs in neurological disorders.