Fructose is widely used as a food ingredient and has potential to increase oxidative stress. Moreover, the beneficial health effects of plant polyphenols are frequently attributed to their potent antioxidant effects. We hypothesized that administration of Globularia alypum (Ga) aqueous extract would reduce metabolic disorders and oxidative stress induced in rats fed a high-fructose diet. Male Wistar rats (n = 24) weighing 242 ± 13 g were divided into 4 groups and fed, during 14 week, diets containing 20% casein and 61% cornstarch (control diet, or C) or fructose (F), and Ga supplementation (0.5%; CGa and FGa). Compared with control group, rats fed a high-fructose diet increased plasma triglycerides (TG; +48%) and very low-density lipoprotein-TG (+45%) levels. In addition, thiobarbituric acid reactive substances were increased in the liver (+31%), heart (+55%), and muscle (+58%). Moreover, activities of superoxide dismutase in the liver and heart, catalase in liver and glutathione peroxidase in the heart were diminished. In the FGa group, a hypertriglyceridemic effect was observed concomitantly with a low level of TG in very low-density lipoprotein and high-density lipoprotein 2, compared with the F group. Thiobarbituric acid reactive substance concentrations were reduced in the kidney (-42%)and muscle (-76%), and antioxidant enzymes activity was increased for superoxide dismutase in the muscle (+81%) and heart (+28%), and for glutathione peroxidase, in the kidney (+70%) and heart (+30%). In conclusion, the Ga extract has a beneficial effect on plasma TG and gives a promising perspective for hypertriglyceridemia treatment. Moreover, in the muscle and kidney, Ga is effective by lowering lipid peroxidation and improves antioxidant enzymes.