Oxidative　stress　has　been　regarded　as　the　leading　mechanism　of　the　hepatotoxicity　of　clofibrate　(CF).　To　achieve　multifunctional　novel　hypolipidemic　agents　with　hypolipidemia,　antioxidant,　and　ameliorating　liver　injury,　clofibric　acid　derivative　hydroxytyrosol-clofibrate　(CF-HT)　was　synthesized　by　molecular　hybridization.　CF-HT　exhibited　significant　hypolipidemia,　reducing　serum　triglyceride　(TG),　total　cholesterol　(TC),　and　malonaldehyde　(MDA)　by　30%,　33%,　and　29%　in　hyperlipidemic　mice　induced　by　Triton　WR　1339.　CF-HT　also　shown　hepatoprotective　effect,　a　significant　decrease　in　hepatic　indices　toxicity　was　observed,　i.e.　aspartate　and　lactate　transaminases　(AST　and　ALT)　activities,　alkalines　phosphatases　(ALP),　and　total　bilirubin　(TBIL)　levels.　The　liver　weight　and　liver　coefficient　were　also　ameliorated.　Serum　superoxide　dismutase　(SOD)　was　significantly　elevated,　and　serum　catalase　(CAT)　and　malondialdehyde　(MDA)　content　were　remarkably　restored.　The　hepatic　glutathione　(GSH)　content　was　obviously　increased　and　hepatic　oxidized　glutathione　(GSSG)　content　was　reduced　dramatically　by　CF-HT,　as　compared　to　the　CF　treated　mice　(p　＜　0.05).　Moreover,　the　histopathological　damage　that　hepatocyte　hyperplasia　and　hypertrophy　was　also　significantly　ameliorated　by　treatment　with　CF-HT.　Therefore,　the　results　indicated　that　CF-HT　exerted　more　potent　hypolipidemic　activity　and　definite　hepatoprotective　effect　which　may　mainly　be　associated　with　its　antioxidative　property　in　mice.