Background: Many reports showed that medicinal plant extracts cause alterations on the shape and physiology of erythrocytes. Objective: The present study seeks to ascertain the osmotic stability of sickle erythrocytes incubated in aqueous extracts of Anacardium occidentale, Psidium guajava, and Terminalia catappa. Materials and Methods: The fraction of erythrocytes lysed when suspended in saline solution of varying concentrations was investigated by spectrophotometric method. The percentage hemolysis of erythrocytes in the control and test samples showed a sigmoidal relationship with increasing concentrations of saline solution. Membrane stability was ascertained as mean corpuscular fragility (MCF) index of erythrocytes incubated in 400 and 800 mg/dL aqueous concentrations of the three plant extracts. Results: The two experimental concentrations of P. guajava and T. catappa protected the erythrocytes against osmotic stress, as evidenced by decreases in the values of MCF compared with the control sample (P < 0.05). However, 800 mg/dL of A. occidentale promoted significant (P < 0.05) distabilization of sickle erythrocytes. Conclusion: Whereas the two experimental concentrations of aqueous extracts of P. guajava and T. catappa stabilized erythrocyte membrane, higher concentration (800 mg/dL) of A. occidentale exhibited no membrane protective effect.