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Sickle cell disorder is a genetic ailment with enormous social and economic burden for patients and caregivers. The most promising management apart from being expensive particularly for poor African people, faces some major incompatibility problems. The patients consequently rely on herbal therapy which could be prepared in single or combination forms to manage the painful episodes and its complications. This present study aimed to formulate polyherbal combination and evaluate three purposively selected plants previously reported for their antisickling activities. The polyherbal products were formulated using both aqueous and 70% ethanol extracts into different combinational ratio with the best in 1:1:1 and evaluated for its antisickling activity. The antisickling activity involved both the inhibitory and reversal effects at varying concentrations from 1.0 mg/ml to 6.0 mg/ml using ciklavit as the positive control. The best inhibitory activity was found in ethanol extract of Piper guineense, Gongronema latifolium and Cymbopogon citratus (PGC) with 70.09 ± 0.67% when compared with the positive control (59.25 ± 0.05%) at 4.0 mg/mg while the reversal ability was 67.87 ± 1.23%. The aqueous extracts of the combinations had activity above 50% with the exception of PGC (2:3:1) which is a little less than 50% (46.67 ± 0.98%) while the highest was 60.02 ± 0.87%. The polyherbal ethanol extract had better effects than the aqueous extract and the standard drug used in this study.