Red yeast (Monascus purpureus) fermented over rice has a limited hypoglycemic activity. To enhance its glucose-lowering effect, we fermented red yeast over waxy barley, a hypoglycemic grain with high levels of fibers and ${eta}$-glucans, and investigated the metabolic effects of red yeast barley (RYB) in high-fat-fed hyperglycemic db/db mice for 6 weeks. The fasting glucose levels were significantly reduced in the RYB group at 6 weeks by 25% (p<0.05), as was the glucose tolerance (-27% of area under the curve in RYB vs. controls, p<0.05). Plasma insulin levels and the expression of PPAR-${gamma}$ were unaltered, however, the phosphorylation activation of hepatic AMP-activated protein kinase (AMPK) was increased significantly in RYB group compared with controls suggesting that hypoglycemic effect of RYB may be achieved by AMPK-dependent mechanism. RYB may be used as a hypoglycemic functional food modulating cellular AMPK activity.