Water decoction made from the seed of Hunteria umbellata is widely used in the traditional management of diabetes mellitus by Nigerian herbalists, particularly, in the southwest region of the country. Recently, a new bisindole alkaloid, erinidine, was isolated but its antihyperglycemic profile remains largely un-investigated scientifically. This forms the basis for the current study which is primarily designed at investigating the antihyperglycemic profile of erinidine and other fractions in both in vitro and in vivo models of diabetes mellitus. In the present study, erinidine was isolated and purified using the earlier described methods and its antihyperglycemic potentials tested in in vitro models such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity, aldose reductase assays and α-glucosidase inhibition assay testings. In addition, 50 mg/kg of erinidine and that of other fractions were evaluated in in vivo models of normal and chemically-induced hyperglycemic rats. Results showed that erinidine was a light yellow, amorphous solid with UV (CHCl3) λ max 256 nm, HRESIMS m/z 382.1881 [(M+H)(+)] (calculated for C22H26N4O2, 382.1876) and melting point of 230 °C. The in vitro study showed the antihyperglycemic action of erinidine to be weakly mediated via α-glucosidase inhibition mechanism as the results for other in vitro tests such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity and aldose reductase assays were all negative. However, the in vivo results showed 50 mg/kg erinidine given per os to normal and alloxan-induced hyperglycemic rats to significantly (p<0.05, p<0.001) attenuate an increase in their post-absorptive blood glucose concentrations after 3 g/kg glucose loading in the rats, suggesting its antihyperglycemic mechanism to be via α-glucosidase inhibition. This result, although, further corroborated the in vitro findings but also suggests that erinidine needs to be biotransformed in vivo for its inhibitory activity on intestinal glucose absorption to become evident. Thus, the present study suggests erinidine to be the possible antihyperglycemic agent in Hunteria umbellata seed extract mediating its antihyperglycemic action via intestinal glucose uptake inhibition.