Nowaday, cancer is one of the main causes of death in the world, and mutants cause the deaths of millions of cancer patients. Given the side effects of drugs in cancer treatment, there is a growing body of research to find drugs with less side effects. The aim of this study was to evaluate the antioxidant effect of different aqueous and alcoholic extracts of safflower petals pigments under drought stress and normal conditions against sodium azide mutant, using Ames test in the absence and presence of microsomes of rat liver (S9). After preparation of different aqueous and alcoholic extracts of safflower petals under drought stress and normal conditions, the anti-mutagenic effect of the extracts was investigated by Ames test. The difference between the averages of revertants per plate in relation to the mutagen was analyzed using SPSS software and one- way ANOVA. The results showed that ethanolic extracts of petals under stress and control group with 90% and 48% inhibition had the highest and lowest anti-mutagenic effects, respectively. The highest level of inhibition was observed in ethanol extract under drought stress, which is in agreement with the results of the microsomal mixture and the findings of previous studies showing that the plant produced antioxidant compounds to decrease the stress effects.