This study aimed to evaluate the potential improvement of Melissa Officinalis  Ethanolic Extract (MEE) against propylthiouracil induced-hypothyroidism. After acclimatization, 50 male Wistar albino rats were randomly divided into five groups; group 1) normal control rats, group 2) normal rats administrated orally with (75 mg/kg) MEE for 60 days, group 3) hypothyroidism-induced rats, group 4) hypothyroidism rats treated orally with Eltroxin^® drug (100 ug/kg), and group 5) hypothyroidism rats treated with MEE (75 mg/kg). The obtained results revealed that hypothyroidism induction resulted in reduction in the thyroid hormones and affect negatively on the liver and kidney tissues as well as deteriorate their oxidative status. MEE therapy succeeded in amelioration of thyroid function towards normal level without any unfavorable effects on the body physiology as it contains many safe phytochemical compounds. In conclusion, MEE possesses anti-hypothyroidism efficacy and antioxidant properties.