Immune-mediated　skin　diseases　have　a　high　prevalence　and　seriously　affect　patients＇　quality　of　life.　Gold　compounds　have　been　considered　promising　therapeutic　agents　in　dermatology,　but　the　high　incidence　of　adverse　reactions　have　limited　their　clinical　application.　There　is　a　great　need　to　develop　more　effective　and　less　toxic　gold-based　drugs.　Gold　nanoclusters　fabricated　by　using　peptides　(pep-AuNCs)　have　appeared　as　potential　biomedical　nanomaterials　because　of　their　excellent　biocompatibility,　ease　of　fabrication　and　unique　physicochemical　properties.　Glutathione　(GSH)　is　an　endogenous　tripeptide　and　has　been　used　for　lightening　the　skin　color.　Therefore,　we　fabricated　a　well-defined　gold　nanocluster　with　GSH　as　an　example　to　explore　the　immunomodulatory　effect　of　AuNCs　on　a　TNF-alpha-treated　human　keratinocyte　cell　line　(HaCaT)　in　vitro,　the　12-O-tetradecanoylphorbol-13-acetate　(TPA)-induced　irritant　contact　dermatitis　(ICD)　model　and　the　oxazolone　(OXA)-induced　psoriatic　model　in　vivo.　The　results　indicated　that　topically　applied　AuNCs　successfully　attenuated　the　severity　of　ICD　and　psoriasis-like　lesions.　In　vitro　and　in　vivo,　AuNCs　effectively　inhibited　the　abnormal　activation　of　the　NF-kappa　B　pathway　and　the　consequent　overexpression　of　proinflammatory　cytokines　in　keratinocytes.　In　particular,　the　transactivation　of　IL-17A,　the　most　important　cytokine　in　psoriasis　pathology,　was　effectively　inhibited　by　AuNCs　treatment.　In　addition,　AuNCs　did　not　show　any　obvious　cytotoxicity　in　HaCaT　cells　at　doses　even　up　to　100　mu　M　and　did　not　induce　any　irritation　in　the　healthy　skin　and　major　organs,　which　indicated　their　favorable　biosafety.　These　results　indicate　that　biocompatible　pep-AuNCs　might　be　a　promising　gold-based　nanomedicine　for　the　treatment　of　inflammatory　skin　diseases.