The corms of Hypoxis argentea are widely used as a traditional remedy for diabetes mellitus in South Africa. In this study, we investigated the effects of non-toxic concentrations (12.5-100 μg mL-1) of the aqueous extract of H. argentea (HAA) corms on glucose uptake, pancreatic beta cell proliferation, and adipocyte differentiation. HAA stimulated glucose uptake in HepG2 cells up to 19.6 % and 17.0 % in L6 myotubes. Live-cell imaging microscopy revealed significant increases (p < 0.001) in total INS-1 cell numbers exposed to HAA, although no effect was observed on adipogenesis in 3T3-L1 pre-adipocytes. HAA produced weak to moderate inhibition of porcine pancreatic α-amylase, α-glucosidase, porcine pancreatic lipase, dipeptidyl peptidase IV (DPP IV) activities, as well as protein glycation. Our results suggest that the acclaimed anti-diabetic effects of H. argentea could be mediated by its promotion of glucose utilization and preservation of pancreatic beta cell populations while preventing fat accumulation in adipocytes.