Sickle cell disease is a common haemoglobinopathy among black African populations. Approximately, 250,000 children are born each year in the world with this disease. The cases of death due to complications of sickle cell disease are mainly registered among children under five, teenagers and pregnant women. Currently, few conventional treatments are available on the market and they are not accessible for everybody. That’s why, many sickle cell patients are turning to traditional medicine. Leptadenia hastata (Asclepiadacae) and Carica papaya (Caricaceae) are plants widely used by traditional healers in the management of sickle cell disea se.The objective of this study is to evaluate the antisickling activity of methanol extracts ofLeptadenia hastata roots and Carica papayagreen epicarp on sickle hemoglobin and identify theactive principles responsible of the observed activity. Reversibility of sickle cell extracts was studied compared with controls (physiological mediumand arginine) in samples of blood from sickle cell homozygotes. Sickling was induced with a 2% solution of sodium metabisulfite. The evaluation was carried out every 30 minutes until 120 minutes.The extracts showed a dose-dependent activity on the reversibility of the sickling of red blood cells with 71% and 87% reversal in 120 minutes of incubation respectively, for L. hastata and C. papaya extracts. A phytochemical screening allowed to make a correlation between flavonoids and antisickling activity.The study justifies the traditional use of Leptadenia hastataroot and epicarp of Carica papaya in the treatment of sickle cell disease.