Eggs contain various bioactive proteins that influence bone health. This study investigated the effects of three water-soluble egg yolk fractions (FA, FB, and FC) and subfractions of FC (FC1 (< 3 kDa) and FC2 (> 3 kDa)) on osteoclastogenesis. FC and its subfractions showed promising osteoclastogenesis inhibitory effects by suppressing osteoclast differentiation in receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW264.7 macrophages. Furthermore, they inhibited RANKL-induced activation of mitogen-activated protein kinase (MAPK) pathway mediators and production of key osteoclastogenic markers in a dose-dependent manner. At 1 000 μg/mL, the FC1 and FC2 fractions resulted in (53.33 ± 9.73)% and (84.00 ± 5.11)% tartrate resistant acid phosphatase-positive osteoclasts, respectively, indicating that the FC1 fraction exhibited stronger inhibitory activity on osteoclastogenesis than the FC2 fraction. Furthermore, the FC1 fraction induced the apoptosis of mature osteoclasts, significantly increasing the proportion of cells in early apoptosis at 10, 100, and 1 000 μg/mL doses ((21.50 ± 1.93)%, (29.17 ± 2.04)%, and (40.40 ± 1.91)%, respectively) and late apoptosis at 1 000 μg/mL ((5.80 ± 1.10)%) compared to the control ((6.37 ± 1.79)% early apoptosis, (0.33 ± 0.58)% late apoptosis). While this study demonstrated the involvement of the MAPK pathway, further investigation is required to confirm their activity in vivo and to identify the components responsible for these effects. The findings of this study may contribute to the development of nutraceuticals and functional food ingredients for improving bone health by using egg yolk-derived fractions.