Anthocyanins are plant-derived pigments, and their aglycons are called anthocyanidin. Anthocyanidins have shown to exhibit various biological functions, such as anti-oxidant effects. However, their structure-activity relationship in bone tissue is not known. In this study, we examined the effects of three anthocyanidins, delphinidin, cyanidin and pelargonidin, on osteoclast differentiation and bone resorption to elucidate the structure-activity relationship. Anthocyanidins suppressed both IL-1 and LPS induced osteoclast differentiation in cocultures of bone marrow cells and primary osteoblasts, and bone resorbing activity in calvarial organ cultures. In osteoblasts, anthocyanidins inhibited prostaglandin (PG) E₂ production via the downregulation of membrane-bound PGE synthase (mPGES)-1, leading to the suppression of PGE₂-mediated receptor-activator of nuclear factorkappa B (NF-κB) ligand (RANKL) expression. In osteoclasts, anthocyanidins inhibited RANKL-induced osteoclast differentiation through the downregulation of osteoclast differentiation marker genes, nuclear factor of activated T-cells 1 (NFATc1), cathepsin K and tartrate-resistant acid phosphatase (TRAP). We further found that anthocyanidins suppressed the inhibitor of NF-κB kinase (IKK) activity in vitro assay, a signal component of NF-κB pathway, suggesting IKK was a novel target molecule of anthocyanidins. We found that delphinidin exerted the most potent inhibitory activity in these experiments, compared with cyanidin and pelargonidin. Anthocyanidins exhibits inhibitory activity in bone resorption, which may depend on the number of hydroxide residues.