Resveratrol　(Res)　is　a　common　natural　polyphenol　that　inhibits　inflammation　and　oxidative　stress　in　Alzheimer＇s　disease　(AD).　However,　the　absorption　efficiency　and　in　vivo　bioactivity　of　Res　are　poor.　High　fat　diet-induced　metabolic　disorders,　including　obesity　and　insulin　resistance,　can　promote　AD-related　β-amyloid　(Aβ)　aggregation,　Tau　protein　phosphorylation　and　neurotoxicity.　Gut　microbiota　play　a　role　in　modulating　metabolic　syndrome　and　cognitive　impairment.　Herein,　flower-like　Res-loaded　selenium　nanoparticles/chitosan　nanoparticles　(Res@SeNPs@Res-CS-NPs)　with　higher　loading　capacity　(64　%)　were　prepared　to　regulate　gut　microbiota　in　cases　of　AD　with　metabolic　disorder.　The　nano-flowers　could　restore　gut　microbiota　homeostasis　to　reduce　lipopolysaccharide　(LPS)　formation　and　LPS-induced　neuroinflammation.　Additionally,　Res@SeNPs@Res-CS-NPs　can　prevent　lipid　deposition　and　insulin　resistance　by　decreasing　Firmicutes　levels　and　increasing　Bacteroidetes　levels　in　the　gut,　further　inhibiting　Aβ　aggregation　and　Tau　protein　phosphorylation　through　the　JNK/AKT/GSK3β　signaling　pathway.　Moreover,　Res@SeNPs@Res-CS-NPs　treatment　was　able　to　regulate　the　relative　levels　of　gut　microbiota　associated　with　oxidative　stress,　inflammation　and　lipid　deposition,　including　Entercoccus,　Colidextribacter,　Rikenella,　Ruminococcus,　Candidatus_Saccharimonas,　Alloprevotella　and　Lachnospiraceae_UCG-006.　Overall,　Res@SeNPs@Res-CS-NPs　significantly　enhances　cognitive　ability　in　AD　mice　with　metabolic　disorder,　highlighting　their　potential　for　preventing　cognitive　impairments　in　AD.　©　2023　Elsevier　B.V.