The approximately three times higher rate of migraine prevalence in women than men may result from the mitochondrial transmission of this disease. Studies with imaging techniques suggest disturbances in mitochondrial metabolism in specific regions of the brain in migraine patients. Migraine shares some clinical features with several mitochondrial diseases and many other disorders include migraine headaches. Epigenetic regulation of mitochondrial DNA (mtDNA) is a matter of debate and there are some conflicting results, especially on mtDNA methylation. Micro RNAs (miRNAs) and long-noncoding RNA (lncRNAs) have been detected in mitochondria. The regulation of the miRNA-lncRNA axis can be important for mitochondrial physiology and its impairment can result in a disease phenotype. Further studies on the role of mitochondrial epigenetic modifications in migraine are needed, but they require new methods and approaches.