Acute and preventive migraine treatment can be quite challenging-the use of several established medications is often limited due to their side effects in the setting of mitochondrial dysfunction and multi-organ disease.<h4>Case presentation</h4>Along with a review of the literature on treatment options in patients with mitochondrial disorders and migraine headaches, we present the case of a 23-year-old male with a homozygous mutation in the mitochondrial single-strand binding protein (<i>SSBP1</i>) with chronic migraine with aura. Here, SSBP1 is linked to migraine disorder.