The presence of excessive osteoclasts is a major factor in skeletal diseases. The present study aimed to discover osteoclast differentiation inhibitors from the basidiomycete <i>Xylodon flaviporus</i>. Seven new drimane sesquiterpenoids (<b>1</b>-<b>7</b>) and 7-ketoisodrimenin-5-ene (<b>8</b>) were obtained and characterized by various spectroscopic methods. The isolated compounds were evaluated for their inhibitory effects against receptor activator of nuclear factor-kappa-B ligand-induced osteoclastogenesis in mouse bone marrow macrophages. Compounds <b>1</b>, <b>3</b>, and <b>6</b> showed potent activities with IC<sub>50</sub> values of 1.6, 0.9, and 2.1 μM, respectively, while <b>4</b>, <b>5</b>, and <b>7</b> exhibited relatively weak activities with IC<sub>50</sub> values of 10.7, 10.1, and 8.5 μM, respectively.