In the present study, regulatory role of vitamin E and curcumin on antioxidant gene (AOG) expression in hypothyroid rat liver is reported. Adult male rats were rendered hypothyroid by administration of 0.05 % 6-propyl-thiouracil in their drinking water, while vitamin E (200 mg/kg body weight) and curcumin (30 mg/kg body weight) were supplemented orally for 30 days. Expression of antioxidant genes (Cu/Zn-superoxide dismutase; SOD1, Mn superoxide dismutase; SOD2, catalase; CAT, glutathione peroxidase; GPx1 and glutathione reductase; GR) was evaluated using RT-PCR and Western blot analyses. The activities of antioxidant enzymes were measured in mitochondrial fraction (MF) and post-mitochondrial fraction (PMF) of rat liver. In addition measurement of glutathione redox status was also carried out in both the fractions. The enhanced transcripts of CAT, GPx1 and GR in hypothyroid rat liver were alleviated by administration of vitamin E and curcumin. Elevated levels of translated product of all AOGs in hypothyroid group were remained unchanged after antioxidant administration. However, enhanced SOD1, GPx1 and decreased GR activities in PMF were normalized by vitamin E and curcumin. Similarly the increased SOD2, GPx1 and decreased CAT activities in MF were also normalized by vitamin E and curcumin supplementation. Administration of vitamin E and curcumin enhanced mitochondrial GSH level; whereas the enhanced GSH level in PMF of hypothyroid rats was alleviated by vitamin E. Thus it can be concluded that besides the antioxidant role of vitamin E and curcumin, they also regulate hepatic antioxidant gene expression in hypothyroid rats.