BACKGROUND: Nowadays, ionizing radiation is used for several applications in 
medicine, industry, agriculture, and nuclear power generation. Besides the 
beneficial roles of ionizing radiation, there are some concerns about accidental 
exposure to radioactive sources. The threat posed by its use in terrorism is of 
global concern. Furthermore, there are several side effects to normal organs for 
patients who had undergone radiation treatment for cancer. Hence, the modulation 
of radiation response in normal tissues was one of the most important aims of 
radiobiology. Although, so far, several agents have been investigated for 
protection and mitigation of radiation injury. Agents such as amifostine may 
lead to severe toxicity, while others may interfere with radiation therapy 
outcomes as a result of tumor protection. Metformin is a natural agent that is 
well known as an antidiabetic drug. It has shown some antioxidant effects and 
enhances DNA repair capacity, thereby ameliorating cell death following exposure 
to radiation. Moreover, through targeting endogenous ROS production within 
cells, it can mitigate radiation injury. This could potentially make it an 
effective radiation countermeasure. In contrast to other radioprotectors, 
metformin has shown modulatory effects through induction of several genes such 
as AMPK, which suppresses reduction/ oxidation (redox) reactions, protects cells 
from accumulation of unrepaired DNA, and attenuates initiation of inflammation 
as well as fibrotic pathways. Interestingly, these properties of metformin can 
sensitize cancer cells to radiotherapy.
CONCLUSION: In this article, we aimed to review the interesting properties of 
metformin such as radioprotection, radiomitigation and radiosensitization, which 
could make it an interesting adjuvant for clinical radiotherapy, as well as an 
interesting candidate for mitigation of radiation injury after a radiation 
disaster.