Plant polyphenols are characterized by a wide range of biological activities, including antioxidant properties, and have a high geroprotective potential. The purpose of this work was to investigate the effect of the extract of rowan berries (Sorbus aucuparia L.) on the lifespan and stress resistance of Drosophila melanogaster with the identification of possible mechanisms of its biological activity. It has been established that an ethanol extract of S. aucuparia berries, the main components of which are rutin and cyanidin-3-rutinoside, has a pronounced antioxidant activity in vitro. At the same time, treatment with rowan berry extract increased the resistance of D. melanogaster males to starvation, but reduced resistance to hyperthermia. In females, the extract reduced resistance to oxidative stress but increased resistance to hyperthermia. The effects of rowan berry extract on longevity depended both on its concentration and on the sex of fruit flies. In response to treatment with rowan berry extract, D. melanogaster males and females showed slight differences in the background level of expression of cellular stress response genes, including heat shock genes (hsp27, hsp68, and hsp83), oxidative stress resistance genes (hif1, nrf2, and sod1), circadian rhythm genes (clk and per), and the longevity gene sirt1, which may explain the differences in the observed effects.