The objectives of the present study were to ascertain the variations in the serum levels of malondialdehyde and total antioxidant status, in head and neck malignancies with different stages, with and without oral antioxidant supplementation, before and after radiotherapy, and to validate the protective effects of an antioxidant supplementation during radiotherapy. The pretreatment values of serum malondialdehyde were significantly raised, while that of serum total antioxidant status were significantly declined in all the stages of head and neck malignancies, when compared with the healthy controls values (P<0.001). A significant correlation was observed related to the studied parameters and different stages of the disease. The study suggests that an oral antioxidant supplementation during radiotherapy is an effective mode in reducing oxidative stress. Antioxidant supplementation during radiotherapy may serve as an adjuvant therapy in malignancies offering a protection to normal cells that may further reduce the risk of developing secondary cancers.