Enteromorpha　prolifera　polyphenols　(EPs)　were　extracted　and　separated,　and　their　antioxidant　activity　and　effect　on　insulin　resistance　(IR)　were　investigated　in　this　paper.　The　2,2-diphenyl-1-picrylhydrazyl　(DPPH·)　radical　scavenging　assay　was　used　to　evaluate　the　in　vitro　antioxidant　capacities　of　EPs;　the　capability　of　EPs　for　reducing　IR　was　evaluated　in　vitro　by　measuring　the　glucose　consumption　of　IR-HepG2　cells.　Experiments　with　diet-induced　obese　(DIO)　mice　were　used　to　evaluate　the　in　vivo　antioxidant　activities　of　EPs　and　their　effects　on　IR　in　vivo.　The　results　showed　that　the　fraction　EP1　had　good　DPPH·　radical　scavenging　ability　with　an　IC50　value　of　1.08　mg/mL.　Compared　to　the　control　group,　EP1　significantly　increased　the　liver　SOD　and　CAT　activities　in　mice　by　25.04%　and　36.28%,　respectively,　and　decreased　the　serum　malondialdehyde　(MDA)　level　by　42.92%.　EP1　improved　IR　states　of　HepG2　cells　and　DIO　mice　significantly　(p<0.05),　reduced　the　homeostatic　model　assessment　(HOMA)-IR　index　by　16.8%,　and　decreased　the　degree　of　obesity　and　reduce　the　fat　percentage　in　DIO　mice　significantly　(p<0.05).　On　the　other　hand,　EP2　was　inferior　to　EP1　in　terms　of　antioxidant　activity　and　IR-improving　effect.　In　summary,　EP1　has　good　in　vitro　and　in　vivo　antioxidant　capacities,　and　can　improve　IR　state　significantly,　which　may　be　associated　with　its　antioxidant　activity　by　suppressing　levels　of　reactive　oxygen　species　(ROS).　©　2016,　Editorial　Board　of　Modern　Food　Science　and　Technology.　All　right　reserved.