Background: Leigh syndrome is one of mitochondrial cytopathy that presents as a neurodegenerative disease with apparent manifestation in the central nervous system. The aim of this study was to describe its neurological symptoms and analyze data related to epilepsy in Leigh syndrome with positive mitochondrial DNA mutation. Methods: Patients who were confirmed as having Leigh syndrome with mitochondrial DNA mutation based on the molecular sequencing analysis were included in our study. A retrospective review of the medical records aided the confirmation of Leigh syndrome, and all analyzed records were sorted respectively as electroencephalography (EEG) findings, semiology, brain imaging findings, and biochemical results. The patients were then divided into two groups depending on the presence of epilepsy. They were further evaluated regarding disease-specific features, including brain magnetic resonance imaging findings and biochemical features. Results: Clinical seizure was observed in 42% of the patients. Generalized seizure was observed in the largest proportion (38%) of them. Some patients presented with involuntary movements which were categorized as unclassified type (23%). A slow and disorganized background on EEG was found in all records, of which 70% were focal and multifocal discharges. Seventy percent of patients with epilepsy were taking fewer than 3 anti-epileptic drugs, and the remaining 30% showed drug resistance. Conclusion: Leigh syndrome with mitochondrial DNA mutation showed a high prevalence of manifestations in the central nervous system, but that of epilepsy was not relatively high. In addition, more than half of the patients were responsive to anti-epileptic drugs, which promise a positive aspect of medical therapeutic effect. Larger group of patients and data on Leigh syndrome with mitochondrial DNA mutation would be helpful to improve the accuracy and specificity of this study.