Although physical exercise is extremely important for health and a good lifestyle, it can trigger oxidative stress, inflammation, and muscle fatigue. The aim of this study was to determine changes in dental tissues and the mandible created by creatines monohydrate (CrM) supplementation together with low and high-intensity exercise (HIE). The study material comprised Balb/c male mices, which were separated into two groups for the application of low and HIE on a running band. CrM supplement was administered together with the exercise. At the end of the experiment period, dental tissue samples were surgically removed and examined histopathologically and immunohistochemically (TNF-α and lL-1β).As a result of the histopathological examinations, in the pulp, oedema, vascular congestion, and capillary dilatation were seen to be statistically significantly increased in the Group 3 mices that performed HIE compared to the control group (p = 0.001, p = 0.003, p = 0.001, respectively). A statistically significant increase was observed in periodontal ligament (PDL) degeneration, and disruption of the continuity and separation of collagen fibers in Group 3 compared to the control group (p = 0.001). In the immunohistochemical examination, TNF-α and IL-1β positivity was observed in Group 3, and this was significantly increased compared to the control group (p = 0.001, p = 0.000).Exposure of the mices to low and HIE caused histological and immunohistochemical changes in dental pulp and PDL, and it was determined that the use of CrM could have a protective effect against these changes. RESEARCH HIGHLIGHTS: The results of this study showed negative effects of HIE in the dental pulp and PDL, which play an important role in dental health. CrM was seen to be effective in preventing these negative effects.