Arsenic (As), a naturally occurring element may induce oxidative stress and is a potent carcinogen. The present study aimed to find the lethal and sub-lethal concentration of arsenic trioxide and explore its effect on survival of fruit fly Drosophila melanogaster. Amelioration using polyphenols (curcumin and soya extract) have been introduced as a successful strategy to overcome this problem. The study showed significant decrease in lifespan of flies treated with arsenic trioxide. 50% mortality was seen in media with 0.5 mM arsenic trioxide and 100% mortality at 0.75 mM. Increased lifespan was observed in medium containing arsenic trioxide (0.55mM) with curcumin (Curcuma longa) and soya extract (Glycine max) respectively. Best survival rate was found in 0.55mM arsenic medium with 1 mM Curcumin and 1.5 mM Soya extract respectively. Lipid peroxidation assay showed significant increase in malondialdehyde (MDA) values in the flies treated with arsenic trioxide as compared to control. The MDA values decreased significantly in flies treated with arsenic mixed with curcumin and soya extract respectively. The results indicate that exposure to sub lethal concentration of arsenic trioxide may cause oxidative stress and affect the lifespan of D. melanogaster. Curcumin and soya extract may help in reducing the impact of oxidative stress and toxicity caused by arsenic trioxide.