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Despite the risk of cyanide poisoning a suitable antidote that can be administered at a reasonable quantity to a large number of individuals is not yet available. This study was carried out to determine the possible hepatoprotective effect of ethanolic extract of Aframomum melegueta seed against cyanide-induced liver injury and its possible antidote effect. Thirty male rats divided into five groups were used for this study. Group 1, received neither cyanide nor the seed extract (Normal control), Groups 2-5 were administered cyanide orally by gavage in form of KCN at a concentration of 4 mg/kg body weight according to body weights as follows; Group 2, received cyanide only (positive control). Group 3 received cyanide and sodium thiosulphate (500 mg/kg body weight) a standard cyanide antidote. (Standard control). Group 4 and 5 were co-treated with cyanide and different doses of the extract three times weekly for the duration of the experiment. Co-treatment with A. melegueta restored the weight loss and the activities of AST, ALT. ALP to levels compared to that obtained in the normal control. In addition co-treatment with A. melegueta modulated the cyanide mediated depletion of the antioxidant capacities of the rats that were exposed to cyanide and the increasing lipid peroxidation profile. The results indicated that ethanolic extract of A.melegueta seed ameliorated cyanide-induced hepatoxicity in rats through their free radical- scavenging mechanisms.