The authors describe the effects of an ethanol extract of maca root on glucose uptake and metabolism in cultured 3T3-L1 adipocytes. The extract stimulates glucose uptake and shares many features of an insulin mimetic: increased phosphorylation of insulin receptor (IR), increased phosphorylation of Akt downstream of IR, and inhibition of glucose uptake by LY294002, an inhibitor of PI3K, which mediates Akt phosphorylation. However, the extract also inhibits mitochondrial oxygen consumption. The effect on glucose uptake is biphasic, and inhibition of mitochondrial respiration is associated with decreased glucose uptake at high concentrations. When the authors examined the effects of a well-characterized mitochondrial poison, oligomycin, for comparison, completely parallel effects on the insulin signaling pathway and the same biphasic effect on glucose uptake were observed. It is concluded that stimulation of the insulin pathway by the extract is an indirect effect of mitochondrial inhibition rather than direct stimulation of the pathway itself. These results have practical implications for assessing the potential benefit of natural products in glucose homeostasis and caution against concentrated extracts from maca for use in humans.