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Glioblastoma is a very aggressive and common brain cancer. Previous studies have shown that changes in the brain's redox biology interfere with behavioral patterns and DNA damage. The results of these studies, however, have been inconclusive. To evaluate the effects of a physical training program on behavioral aspects, redox and genomic stability parameters in animals exposed to an experimental model of GBM. Forty-seven male C57BL/6J mice aged sixty days were randomly selected and divided into two groups (GBM and sham/placebo surgery), which were subsequently divided into four groups: untrained sham (Sut, n = 10), untrained GBM (Gut, n = 15), trained sham (Str, n = 10), and trained GBM (Gtr, n = 12). The trained animals performed 3 sessions, followed by a rest day, of moderate aerobic exercise on a treadmill for four consecutive weeks, while the untrained animals were kept in boxes during the experimental period. Behavioral indicators were evaluated with open field and rota rod tests. After the last training session, the animals were euthanized and brain, liver, bone marrow, and blood were collected for analysis of redox and genomic instability markers. The results showed higher latency values were sustained by the exercise in Gtr. The elevated levels of total reactive oxygen species in the parietal tissue of Gut animals were reversed after physical training. The Gtr group had a lower tail intensity. Physical exercise is a promise as an adjunctive therapy for the management of GBM by modulating redox parameters in the parietal tissue and reduces the genomic instability in liver and blood.