Osteoporosis is a debilitating disease caused by decreased bone density. Compounds with anti-osteoclastic activity, such as bisphosphonates, may help in the prevention and treatment of osteoporosis. Herein, we determined the inhibitory effects of ginger hexane extract (GHE) on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. The results showed that GHE (1) suppressed osteoclast differentiation and the formation of actin rings; (2) inhibited the expression of Nfatc1, a master transcriptional factor for osteoclast differentiation, in a dose-dependent manner (10-20 μg/mL); and (3) inhibited other osteoclastogenesis-related genes, such as Oscar, Dc-stamp, Trap, and Mmp9. These findings suggest that GHE may be used to prevent and treat osteoporosis by inhibiting osteoclast differentiation.