Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with highly heterogeneous manifestations. Curvilinear hyperintensity along the corticomedullary junction on diffusion-weighted images (DWI) is a vital clue for diagnosing NIID. DWI hyperintensity tends to show an anterior-to-posterior propagation pattern as the disease progresses. The rare cases of its disappearance may lead to misdiagnosis. Here, we reported a NIID patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like (MELAS-like) episode, and reversible DWI hyperintensities. A review of the literature on NIID with MELAS-like episodes was conducted. A 69-year-old woman stated to our clinics for recurrent nausea/vomiting, mixed aphasia, altered mental status, and muscle weakness for 2 weeks. Neurological examination showed impaired mental attention and reaction capacity, miosis, mixed aphasia, decreased muscle strength in limbs, and reduced tendon reflex. Blood tests were unremarkable. The serological examination was positive for antibody against dipeptidyl-peptidase-like protein 6 (DPPX) (1:32). Brain magnetic resonance imaging (MRI) revealed hyperintensities in the left temporal occipitoparietal lobe on DWI and correspondingly elevated lactate peak in the identified restricted diffusion area on magnetic resonance spectroscopy, mimicking the image of MELAS. Skin biopsy and genetic testing confirmed the diagnosis of NIID. Pulse intravenous methylprednisolone and oral prednisolone were administered, ameliorating her condition with improved neuroimages. This case highlights the importance of distinguishing NIID and MELAS, and reversible DWI hyperintensities can be seen in NIID.