This study investigated antimalarial and antioxidant activity of Vernonia amygdalina ethanol leaf extract on mice infected with plasmodium berghei. LD50 value of extract was greater than 3200mg/kg/bt. DPPH and hydrogen peroxide activity showed concentration dependent increase. S Vernonia ignificant (p<0.001) suppression of parasite was 63.7% and 77.0% at 150mg/kg and 300mg/kg respectively was recorded in the suppressive test while 75.8% suppression of parasitaemia was recorded at 300mg/kg of extract in established malaria infection and prolonged their survival time up to 28 days compared to negative control which died within 13 days. Increase in reduced glutathione and decrease in malondialdehyde activity indicate reduction in oxidative stress while decrease in catalase activity implies oxidative stress. The extract increased packed cell volume and red blood cell count of mice. V. amygdalina leaf extract possesses antioxidant and potent antimalarial potentials which can be harnessed for the production of antimalarial pharmaceuticals and can be further accessed for treatment of anemia.