Hashimoto's encephalopathy is usually underdiagnosed and untreated because of complex neuropsychiatric manifestation. We report a case of an adolescent female with Hashimoto's encephalopathy who responded well to a combination of aspirin and levothyroxine. A 16-year-old girl presented at psychiatric emergency services with a depressive episode, menstrual irregularities, and a 5-month past history of thyroid swelling. On clinical examination, she was in a euthyroid state with insignificant neurological history. However, her previous investigation revealed a hypothyroid state. Her magnetic resonance imaging findings demonstrated infarcts in the bilateral gangliocapsular region and left frontal periventricular deep white matter lesion. Ultrasonography of the thyroid and fine needle aspiration cytology confirmed lymphocytic thyroiditis. Anti-thyroid peroxidase (289 IU/ml) antibody titer was elevated (289 IU/mL). Her depressive symptoms responded well to antidepressants, mood stabilizers, nonsteroidal anti-inflammatory drugs, and levothyroxine. She remained in the euthyroid state and then in the euthymic state for 3 years. Hashimoto's encephalopathy is steroid-responsive encephalopathy. Most researchers have observed a dramatic response to steroids with or without levothyroxine. A clinician may consider aspirin as an alternative to a steroid in long-term management to avoid steroid-related side effects and contraindications.