Regulation of osteoclastogenesis and bone-resorbing activity can be an efficacious strategy fortreating bone loss diseases because excessive osteoclastic bone resorption leads to thedevelopment of such diseases. Here, we investigated the role of (-)-tubaic acid, a thermaldegradation product of rotenone, in osteoclast formation and function in an attempt to identifyalternative natural compounds. (-)-Tubaic acid significantly inhibited receptor activator ofnuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation at both the early and latestages, suggesting that (-)-tubaic acid affects the commitment and differentiation of osteoclastprogenitors as well as the cell-cell fusion of mononuclear osteoclasts. (-)-Tubaic acid attenuatedthe activation of extracellular signal-regulated kinase (ERK) and expression of nuclear factor ofactivated T-cells cytoplasmic 1 (NFATc1) and its target genes in response to RANKL. Furthermore, a pit-formation assay revealed that (-)-tubaic acid significantly impaired the boneresorbingactivity of osteoclasts. Our results demonstrated that (-)-tubaic acid exhibits antiosteoclastogenicand anti-resorptive effects, indicating its therapeutic potential in themanagement of osteoclast-related bone diseases.