Aβ　aggregation-related　neuroinflammation　and　imbalance　of　brain　glucose　homeostasis　play　important　roles　in　the　pathological　process　of　Alzheimer＇s　disease　(AD).　Chlorogenic　acid　(CGA)　is　one　of　the　most　common　dietary　polyphenols　with　neuroprotective　effects.　However,　due　to　the　low　bioavailability　of　CGA,　its　application　dose　is　usually　high　in　vivo.　In　our　previous　study,　the　spherical　selenium　nanoparticles　act　as　drug　carriers　to　improve　the　bioactivity　of　resveratrol.　Here,　the　brain-targeting　peptide　(TGN　peptide)　and　CGA　were　used　to　prepare　a　new　flowerlike　selenium　nanocluster　(TGN-CGA@SeNCs)　for　enhancing　the　bioavailability　of　CGA.　After　decoration　on　selenium　nanoclusters,　the　solubility　and　stability　of　CGA　was　obviously　increased.　Oral　administration　of　a　low　dose　of　CGA　(80　mg/kg/body　weight)　only　slightly　inhibited　Aβ　aggregate-related　neuroinflammation　and　glucose　homeostasis　disorder　in　the　brain.　Moreover,　CGA　showed　less　effect　on　increasing　the　diversity　and　richness　of　gut　microbiota.　At　the　same　concentration,　the　CGA-modified　selenium　nanocluster　(CGA@SeNCs)　and　TGN-CGA@SeNCs　showed　better　function　in　ameliorating　the　gut　microbiota　disorder.　Especially,　TGN-CGA@SeNCs　significantly　increased　the　relative　abundance　of　Turicibacter,　Colidextribacter,　Ruminococcus,　Alloprevotella,　and　Alistipes　against　oxidative　stress,　inflammation,　and　glucose　homeostasis　imbalance.　Notably,　only　TGN-CGA@SeNCs　can　transport　through　the　blood-brain　barrier　(BBB),　and　TGN-CGA@SeNCs　showed　better　effects　than　CGA@SeNCs　in　regulating　Aβ　aggregation　and　improving　brain　glucose　homeostasis.　These　results　broadened　the　application　of　TGN-CGA@SeNCs,　effectively　improving　the　bioactivity　of　CGA,　which　also　lowers　the　CGA　dose　for　preventing　AD　progression.　©　2023　American　Chemical　Society.