Malaria has been reported to be one of the most debilitating illnesses of all time and is the most common parasitic disease in sub-Saharan Africa. Methanol extract of the four parts of Ficus sycomorus plant (leave, fruits, stem-bark and roots) were screen for in vitro anti-plasmodial activity using Plasmodium falciparum. The IC50 revealed that the fruits and leave extract have an IC50 ˃ 186µg while stem-bark and roots were discovered to be the most active with IC50 of 20.4µg. In vitro anti-plasmodial activity of organic solvent extracts (Hexane, ethylacetate and saturated butanol) of the methanol root extract revealed IC50 of 40µg, 20.4µg and 20.4 µg respectively. In vivo anti-plasmodial activity of the saturated butanol extract of the root was investigated in albino mice. Thirty (30) mice were inoculated with the parasitized donor erythrocytes containing Plasmodium berghei. One week after parasite inoculation, the animals were randomly distributed into six groups of five mice each. Group 1 served as negative control (not treated), groups 2 to 5 were experimental groups and were administered 20%, 40%, 60% and 80% of the LD50 (31mg, 62mg, 93mg and 124mg), while group 6 served as positive control (treated with artesunate). The mice were treated orally for seven consecutive days once daily. The results showed that the saturated butanol has anti-plasmodial activity in mice with percentage parasitemia inhibition of 50.6%, 80.8%, 100%, 100% and 100% for groups 2 to 5 and artesunate respectively. The results suggest that the plant have potential for the development of a novel anti-malarial agent.