Inflammation-induced　bone　erosion　is　a　major　pathological　factor　in　several　chronic　inflammatory　diseases　that　often　cause　severe　outcomes,　such　as　rheumatoid　arthritis　and　periodontitis.　Plenty　of　evidences　indicated　that　the　inflammatory　bone　destruction　was　attributed　to　an　increase　in　the　number　of　bone-resorbing　osteoclasts.　However,　anti-resorptive　therapy　alone　failed　to　prevent　bone　loss　in　an　inflammatory　condition.　Conventional　anti-inflammation　treatments　are　usually　intended　to　suppress　inflammation　only,　but　ignore　debilitating　the　subsequent　bone　destruction.　Therefore,　inhibition　of　proinflammatory　activation　of　osteoclastogenesis　could　be　an　important　strategy　for　the　development　of　drugs　aimed　at　preventing　inflammatory　bone　destruction.　Methods:　In　this　study,　we　synthesized　a　peptide　coated　gold　cluster　to　evaluate　its　effects　on　inflammatory　osteoclastogenesis　in　vitro　and　inflammation-induced　bone　destruction　in　vivo.　The　in　vitro　anti-inflammation　and　anti-osteoclastogenesis　effects　of　the　cluster　were　evaluated　in　LPS-stimulated　and　receptor　activator　of　nuclear　factor　kappa　B　ligand　(RANKL)　stimulated　macrophages,　respectively.　The　LPS-induced　expression　of　crucial　pro-inflammation　cytokines　and　RANKL-induced　osteoclastogenesis　as　well　as　the　activation　of　NF-kappa　B　pathway　in　both　situations　were　detected.　The　inflammation-induced　RANKL　expression　and　subsequent　inflammatory　bone　destruction　in　vivo　were　determined　in　collagen-immunized　mice.　Results:　The　gold　cluster　strongly　suppresses　RANKL-induced　osteoclast　formation　via　inhibiting　the　activation　of　NF-kappa　B　pathway　in　vitro.　Moreover,　treatment　with　the　clusters　at　a　dose　of　5　mg　Au/kg.　bw　significantly　reduces　the　severity　of　inflammation-induced　bone　and　cartilage　destruction　in　vivo　without　any　significant　toxicity　effects.　Conclusion:　Therefore,　the　gold　clusters　may　offer　a　novel　potent　therapeutic　stratagem　for　inhibiting　chronic　inflammation　associated　bone　destruction.