Amoebiasis, classified as the third intestinal parasitic infection, represents a public health problem in low-income countries where hygiene and sanitation conditions are poor. With the resurgence of resistant pathogenic strains as well as ancestral considerations in developing countries such as Cameroon, many people rely on medicinal plants to treat a plethora of diseases. This work aimed to highlight the anti-amoebic and anti-oxidant potential of Codiaeum variegatum extracts and fractions. The anti-amoebic potential of C. variegatum was assayed on the polyxenic culture of the clinical isolates of E. histolytica. Then, the anti-oxidant potential of the ethanolic/hydroethanolic extracts and fractions was evaluated through DPPH radical scavenging, iron reduction (FRAP), lipid peroxidation inhibitory potential and total antioxidant capacity tests followed by the determination of phenolic compound and flavonoid content. It was found that the fractionation process decreased the amoebicidal activities of C. variegatum leaf extracts. However hydroethanolic extract (CI 50 : 10.08 ± 0.42, 5.18 ± 0.09, 5.18 ± 0.09 µg/mL respectively after 24, 48 and 72 hours) was more active than ethanolic extract (CI 50 : 15.59 ± 6.17; 9.61 ± 2.37; 6.26 ± 3.22 µg/mL respectively after 24, 48 and 72 hours). Interestingly, the activities of hydroethanolic extract were significantly non-different compared to metronidazole CI 50 : 8.42 ± 0.44, 6.45 ± 0.22 and 3.42 ± 0.33 µg/mL, respectively after 24, 48 and 72 hours). Ethanolic extract and EF5 showed higher Phenolic compound contents and higher antioxidant activity How to cite this paper: Nsangou