Hypoglycemia is rare in patients without diabetes mellitus. Methadone is a synthetic μ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of opioid dependence. Here, we report a case of a 31-year-old man who presented with recurrent hypoglycemic events that resolved on discontinuation of methadone. Thus, if hypoglycemia occurs while a patient takes methadone, the amount should be reduced or replaced with another opioid before a full investigation for inappropriate hyperinsulinism is initiated.