Aims: In traditional medicine, several plant species from Rutaceae’s family have been used to treat sickle cell anemia. However, more studies are needed to corroborate the antisickling activity of Zanthoxylum leprieurii species. The objective of this paper was to evaluate the sickling cell inhibition and radical scavenging activities of hydroethanolic and aqueous extracts of Zanthoxylum leprieurii’s bark, a plant species used in the management of sickle cell anemia in eastern Côte d’Ivoire. Methods: Hydroethanolic and aqueous extracts of the stem bark of Zanthoxylum leprieurii were prepared. Qualitative and quantitative phytochemical tests were carried out. In addition, diphenyl 1, 2 picrylhydrazyl (DPPH) was used to determine the antioxidant potential of these two extracts. The antisickling activity of two extracts was determined by the Emmel method. Results and Discussion: Zanthoxylum leprieurii’s barkextracts have demonstrated antioxidant property. The IC50 value of the hydroethanolic extract (0.308±0.06) was lower than that of the decocted (0.434 ±0.06). At 10 mg/mL, the sickling cell inhibition of DZL was 81% ±2.66 while EZL was 89% ±0.44. The presence of alkaloids, sterols, Polyterpenes and phenolic compounds in both extracts could explain the sickling inhibition activity of these extracts. All the extracts revealed an antioxidant and antisickling activities higher than the standard. Conclusion: The hydroethanolic extract (EZL) demonstrated a higher antisickling activity and exhibited a better free radical scavenging activity. The use of Zanthoxylum leprieurii’s bark in the traditional management of sickle cell anemia is justified.