The effectiveness of mouthwash protocols in preventing gamma irradiation therapy damage to the ultimate tensile strength (UTS) of enamel and dentin is unknown. It was hypothesized that the use of chlorhexidine and fluoride mouthwash would maintain the UTS of dental structures. One hundred and twenty teeth were divided into 2 groups irradiated (subjected to 60 Gy of gamma irradiation in daily increments of 2 Gy) and non-irradiated. They were then subdivided into 2 mouthwash protocols used 3 times per day 0.12% chlorhexidine, 0.05% sodium fluoride, and control group (n = 10). The specimens were evaluated by microtensile testing. The results of the Tukey test (p < 0.05) indicated that the gamma irradiation therapy significantly reduced the UTS of the enamel, crown, and root dentin. Macromolecular alterations were suggested by optical retardation data in dentin. Structural alterations, in both substrates, were detected by scanning electron microscopy analysis. Mouthwash with 0.12% chlorhexidine partially prevented the damage to the mechanical properties of the irradiated crown dentin, whereas the 0.05% sodium-fluoride-irradiated enamel showed UTS similar to that of non-irradiated enamel.