The phenol content of vegetable oil and its antioxidant activity are of primary interest for human health. Oilseed species are considered important sources of these compounds with medicinal effects on a large scale. Total phenol content (TPC) and antioxidant activity (AA) of safflower oil were previously studied. Nevertheless, there is no report on genotypic differences and antiaging activity of safflower oil. The aim of this study was to determine the TPC, diphenyl-picrylhydrazyl (DPPH), and antiaging activity on three respective accessions from Syria, France, and Algeria of seed oil of safflower grown under semi-arid conditions during 3 consecutive years (2015, 2016, and 2017). The results showed that phenol content as well as antioxidant and antiaging activity varied according to both genotype and years. In 2017, the mean value of TPC in oil seed was two times higher than in 2015 and 2016. Moreover, accessions presented different TPC values depending on the year. The highest antioxidant activity was observed among accessions in 2017 compared to 2015 and 2016. As expected, a positive correlation was found between TPC and antioxidant activity. The inhibition in the collagenase assay was between 47% and 72.1% compared to the positive control (83.1%), while inhibition in the elastase assay of TPC ranged from 32.2% to 70.3%, with the positive control being 75.8%. These results highlight the interest of safflower oil as a source of phenols with valuable antioxidant and antiaging activity, and uses for cosmetics.