Neurodegenerative　diseases　have　become　a　huge　challenge　to　public　health,　such　as　Alzheimer＇s　and　Parkinson＇s　diseases.　Microglia　driving　inflammation　in　the　central　nervous　system　(CNS)　has　been　involved　in　the　pathological　process　of　these　disorders　and　could　be　novel　therapy　target.　However,　traditional　anti-inflammatory　drugs　are　not　effective　in　alleviating　neuroinflammation.　In　this　study,　a　potential　neuroprotective　effect　of　a　peptide-templated　gold　nanocluster　(Au(25)Sv(9))　was　investigated.　Firstly,　effect　of　the　nanocluster　on　cytotoxins＇　secretion　of　activated　BV-2　microglia　cells　was　assessed.　Results　indicated　Au25Sv9　nanocluster　effectively　attenuated　the　cytotoxicity　of　stimulated　microglia　cells　towards　neuronal　cells.　And　the　underlying　mechanism　of　action　was　illuminated　preliminarily.　The　secretions　of　IL-6,　TNF-alpha　and　NO　in　activated　microglia　cells　were　inhibited　by　the　nanocluster　in　a　dose-dependent　manner　via　suppressing　the　activation　of　NF-kappa　B　and　p38　pathways.　Moreover,　the　ability　of　the　nanocluster　to　protect　neuronal　cells　to　against　microglial　cytotoxins　was　also　evaluated.　Treating　neuronal　cells　with　the　nanoclusters　could　protect　them　from　cytotoxicity　induced　by　supernatants　of　stimulated　microglia　cells　through　up-regulating　of　hemeoxygenase-1　(HOX-1).　This　study　suggested　the　peptide-templated　gold　nanocluster　is　able　to　reduce　microglia-mediated　cytotoxicity　to　neuronal　cells　and　possess　direct　neuroprotective　properties　simultaneously.　We　deduce　the　gold　nanocluster　would　be　an　effective　therapeutic　approach　to　against　neuroinflammation　driving　neurodegenerative　diseases　in　the　future.