Background: Chromolaena odorata (C. odorata) is a medicinal plant with hypoglycemic effect known in traditional medicine. The present study investigated the in vitro antioxidant and in vivo anti-hyperglycemic effect of the methanol root extract of C. odorata in rats. Methods: Phytochemical compositions were evaluated, using standard procedures while the antioxidant activities were examined, using 1, 1-Diphenyl-2-Picrylhydrazyl (DPPH) Free Radical Scavenging and Ferric Reducing Power (FRAP) assays. Twenty albino rats were administered 120 mg/kg of body weight (bw) alloxan and were divided into four groups of five animals each. Groups A to D were treated with 2 ml/kg of normal saline, 300 mg/kg, 500 mg/kg bw extract and 5 mg/kg bw glibenclamide, respectively, through oral route for 14 days. Blood samples were collected and prepared for the analysis of serum lipids profile. Results: The extract contained tannins (54. 76± 4. 08 mg/100 g), saponins (322. 78± 17. 35 mg/100 g), glycosides, alkaloids (74. 34± 6. 08 mg/100 g), flavonoids (79. 63± 4. 55 mg/100 g), phenols (154. 32± 11. 21 mg/100 g), glycosides, steroids and reducing sugar. The extract promoted the inhibition of DPPH radicals with IC50 values of 191. 68± 1. 68 µ g/mL. In comparison with the untreated controls, total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and triglycerides were significantly reduced (P<0. 05) following treatment with C. odorata extract while High Density Lipoprotein (HDL)-cholesterol, was significantly increased. Conclusion: The C. odorata extract exhibited antioxidant and hypolipidemic effects in alloxan-induced diabetic rat, thus could be considered as a natural product in the management of dyslipidemia secondary to diabetes.