The search for drugs that affect the radioresistance of an organism is an urgent task of radiobiology and medicine. The effects of retinoic acid, enoxacin, KN-93, and UNC-0646 on resistance to γ-irradiation at doses of 120 and 800 Gy, as well as on the level of DNA damage and the efficiency of DNA repair were studied for the first time using the Drosophila melanogaster model. The results of the study indicate an increase in the radiosensitivity of flies after the addition of all four selective drugs to the medium at a young and mature age. Median and maximum survival after substance treatment was reduced to 50% (p < 0.0001). In addition, KN-93 and UNC-0646 exacerbated radioinduced DNA damage in males, but resulted in a moderate protective effect in females. At the same time, a protective effect of enoxacin against DNA damage was found in males. The influence of the studied drugs on the survival of Drosophila can be associated with the period of use of pharmacological compounds, the amount of their intake into an organism of males and females, the selected doses and irradiation regimens.