Background <p>To investigate the preventive efficacy of methylsulfonylmethane (MSM) on alveolar bone destruction in rats with periodontitis.</p> Methods <p>Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-MSM. Periodontitis was induced by placing 4.0 silk sutures in the subparamarginal position on the necks of the mandibular first molars and applying the suture for 5 weeks. The Ep-MSM group was given 500&#xa0;mg/body weight/day MSM intraperitoneally for 35 days. At the end of the study, bilateral mandibular samples were taken. Periodontal bone loss was measured through histologic sections. Histomorphometric and immunohistochemical (receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG)) evaluations were performed on right mandibular tissue samples, and biochemical (interleukin (IL)-1 beta (β)/IL-10, malondialdehyde (MDA), glutathione (GSH), oxidative stress index (OSI)) evaluations were performed on left mandibular tissue samples.</p> Results <p>No significant difference was found between the groups in IL-1β and IL-1β/IL-10 values ​​(<i>p</i> &gt; 0.05). A significant decrease in IL-10 levels was observed in the Ep-MSM and Ep groups compared with the control group (<i>p</i> &lt; 0.05). MDA levels significantly increased in the Ep and Ep-MSM groups compared with the control group, and GSH levels significantly decreased in the Ep group compared with the other groups (<i>p</i> &lt; 0.05). OSI values ​​were significantly higher only in the Ep group (<i>p</i> &lt; 0.05). RANKL levels showed a significant increase in the Ep group compared with the other groups. OPG levels were significantly increased only in the Ep-MSM group (<i>p</i> &lt; 0.05).</p> Conclusions <p>The results of this study may suggest that MSM has preventive effects on alveolar bone loss and oxidative stress.</p>