Sickle cell disease (SCD) is traditionally treated in Nigeria by the Traditional Medical Practitioners (TMPs) with medicinal plants and other plant products. One of the herbs commonly used singly or in combination with other plant materials is Khaya, which is widely distributed in Africa, with three species existing in Nigeria. These are Khaya senegalensis A. Juss (KS), Khaya grandifoliola (WELW) CDC (KG) and Khaya ivorensis A. Chev. (KI). In this study we evaluated the anti-sickling activities of the leaf extracts of the three Khaya species leaves with a view to authenticating the ethnomedicinal claims, and assess the proximate as well as the elemental constituents that may contribute to the properties. Dried leaves of the Khaya species were extracted by cold maceration and Soxhlet methods using water, ethanol and petroleum spirit as extractives. Filtered extracts were concentrated in vacuo at 40oC and dried in a lyophilizer. Inhibitory and reversal models were employed to evaluate their anti-sickling effects on Hb SS red blood cells following standard procedures. Proximate and elemental analysis were determined using the simple analytical procedure as described by the Association of Official Analytical Chemistry (AOAC) of 1987, 13th Edition Washington DC P1094 and Dry Ashing method of AOAC 2006 respectfully. Anti-sickling results showed that the Soxhlet ethanol extracts of the Khaya species demonstrated significant (p≤0.05) ability to reverse and inhibit the sickling of red blood cells in-vitro with KI having the highest inhibitory and reversal of 60.04+1.77% and 74.97+2.23% respectively at 4 mg/ml concentration. The proximate analysis revealed the richness of the Khaya leaves in minerals, proteins and carbohydrates. Khaya leaves contained calcium, magnesium, sodium, phosphorus, and other essential elements within the limits of dietary requirement. Khaya species could therefore be recommended for further development into herbal remedy in the management of sickle cell disease.