Five experiments were conducted to evaluate the dietary effects of vitamin E, vitamin C and selenium on mitigation of mercury toxicity in olive flounder and mice. In the first experiment, six experimental diets were prepared in a 2×3 factorial design; these were three levels of vitamin E (0, 100, or 200 mg/kg diet) and two levels of mercury (0 or 20 mg/kg) for olive flounder. Results showed that dietary supplementation of vitamin E (at 100, or 200 mg/kg) increased growth in both presence and absence of Hg. Also, vitamin E at 100, or 200 mg/kg inorganic reduced mercuty bioaccumulation for Hg toxified fish (20 mg/kg) groups. In the second experiment, vitamin C (0, 100, or 200 mg/kg diet) and mercury (0 or 20 mg/kg) were added to the basal diet for olive flounder in a 2×3 factorial design (six experimental diets). Results revealed that dietary vitamin C at 100 or 200 mg/kg resulted in high growth and a low mercury accumulation for Hg toxified fish (20 mg Hg /kg). In the third experiment, synergistic effects of dietary vitamin E (0, 100, or 200 mg/kg diet) and selenomethionine (0, 2 and 4 mg/kg) in a 3×3 factorial design were evaluated in the mercury toxified (20 mg/kg) olive flounder. Results showed that dietary vitamin E more than 100 mg/kg diet with 2 or 4 mg/kg selenomethionine-supplementation could have synergistic effects on growth and liver mercury bioaccumulation in juvenile olive flounder. In the fourth experiment, synergistic effects of dietary vitamin C (0, 200, or 400 mg/kg diet) and selenomethionine (0, 2 and 4 mg/kg) in a 3×3 factorial design were evaluated in the mercury toxified (20 mg/kg) olive flounder. Results indicated the synergistic effects on growth and mercury accumulation in muscle, liver and kidney for fish fed diets containing 400 mg/kg vitamin C with 2 or 4 mg selenomethionine. In the fifth experiment, a 3×2 factorial design was used with three levels of Hg (0, 50 or 500 μg/kg and two levels of Se (0 or 2 mg/kg) with olive flounder muscle powder in constant combination with vitamin C and E (C: 0 or 400 mg/kg; vitamin E: 0 or 200 mg/kg) in mice. Results showed that dietary selenomethionine (2 mg/kg), vitamin C (400 mg/kg) and vitamin E (200 mg/kg) had no effect on reducing the mercury bioaccumulation in tissues but reduced the serum lipid peroxidation as well as prolonged the cumulative survival rate in terms of high Hg exposures in mice. Therefore, these result indicate that dietary antioxidants such as vitamin C, E and selenium could reduce bioaccumulation of mercury in fish but not mice, hence these antioxidants can reduce the toxicity effects of mercury in both fish and mice models.