The effect of soil and foliar iron (Fe) application on the activity of some antioxidant enzymes and plant metabolites of Carthamus tinctorius L. (IL111), under water stress conditions was tested. The results showed that under drought stress conditions, the activity of ascorbate peroxidase, superoxide dismutase, polyphenol oxidase and catalase enzymes increased with soil application of Fe. In contrast, the activity of peroxidase enzyme under drought conditions increased with foliar application of Fe treatments. In general, leaf total soluble proteins, proline and malondialdehyde amounts were affected by interaction effects of drought stress and Fe. The results showed that leaf total soluble proteins had a positive reaction to soil and foliar applications of Fe. The result of this interaction effects showed that soil application of Fe is able to decrease malondialdehyde amount under water stress conditions. In addition, it was indicated that soil application of Fe in drought stress conditions lead to increasing proline. In conclusion, soil and foliar application of Fe during drought stress may counteract negative effects of such stress and enhance safflower tolerance to drought by increasing some antioxidant enzymes and plant metabolites (organic compounds such as proline and soluble proteins).