New advances in the area of deciphering the mechanism for a possible modification of the biological effects of radiation exposure at the genetic level make it possible to distinguish the group of radiation protective agents having their own specific features in the implementation of their beneficial effects. The mechanism of the radioprotective action of bioflavonoids is worthy of a detailed analysis in view of their great biological importance. Radiobiological studies show that antioxidants can reduce the radiation damage to membranes and favor more adequate energy dependent adaptive and reparative processes after the exposure to radiation. Bioflavonoids are significant component of “biological protection” for a enhance of resistance of the body to environmental factors that are adverse for human health, including ionizing radiation, with reducing the risk of carcinogenic effects and decreasing the biological age. The best practical value of bioflavonoids, can be considered as the agents for prophylaxis against the development of oxidative stress. These are the reasons why the administration of natural antioxidants have a pathogenetic justification for exposures to chronic (months, years) low-rate-dose ionizing radiation. These agents were previously and are currently being developed for use during long-term, low-ratedose exposures to radiation, under conditions of long space missions. Acting as low-dose stressors through a hormetic mechanism and a “substrate” support of adaptive shifts radiomodulators results in an increase in the antioxidant defense of the body and the rearrangement of its functioning in the new environment with the modulation of gene expression of antioxidant response elements by activation of Nrd2/KeapI and Sirtuin/FoxO pathways and a decrease in the transcription factor NF-κB.