Flavonoid-rich foods intake has been associated with lower risk of non-communicable chronic diseases. Quercetin is the most abundant flavonoid in nature (fruits, vegetables, leaves and grains) as well as the most consumed flavonol. This study aims to investigate the potential effects of its conjugated form quercetin-3-O-glucoside (or isoquercetin) on glucose metabolism in rats and Caco-2 cells. To analyse the effect of quercetin-3-O-glucoside on postprandial hyperglycemia, an oral glucose tolerance test (OGTT) was conducted in Wistar rats. Additionally, Caco-2 cells were used to determine the effect of quercetin- 3-O-glucoside (30 to 60 ¿M) on mRNA expression of genes involved in glucose uptake by RT-PCR. Thereby, in vivo studies demonstrated that quercetin-3-Oglucoside decreased blood glucose levels evaluated by OGTT in rats. Furthermore, in the presence of Na+, quercetin-3-O-glucoside inhibited methylglucoside (MG) uptake in enterocytes and both sodium dependent glucose transporter-1 (SGLT1)- and glucose transporter-2 (GLUT2)-mediated glucose uptake were downregulated in Caco-2 cells incubated with quercetin-3-O-glucoside. In summary, our results show that quercetin-3-O-glucoside improves postprandial glycemic control in rats and reduces sugar uptake in Caco-2 cells, possible by decreasing the expression of glucose transporters (SGLT1 and GLUT2) according to the results obtained through RT-PCR.