Background: Reversible splenial-lesion syndrome (RESLES) is a relatively rare and underrecognized clinical-imaging syndrome involving the splenium of the corpus callosum (SCC). RESLES can be caused by various etiologies. Case description: An 18-year-old man with no previous history of neurological or psychiatric disorders presented to our hospital with headache, intermittent blurred vision, and limb weakness after 150 days of recreational nitrous-oxide abuse. The patient's serum vitamin B12 concentration was normal, and magnetic-resonance imaging (MRI) examination revealed isointensity on T1-weighted imaging (T1WI) of the corpus callosum and high signal intensity on T2WI, T2FLAIR, and diffusion-weighted MRI (DWI); thus, a diagnosis of RESLES was established. The patient received 0.5 mg of mecobalamin daily and nitrous oxide was discontinued. After 4 weeks, the patient's symptoms disappeared and the imaging examination revealed normal findings. Conclusion: We report for the first time a case of headache, blurred vision, and hallucination caused by RESLES associated with nitrous-oxide abuse. In cases of headaches and hallucinations of unknown etiology, the possibility of RESLES caused by nitrous oxide abuse should be considered.