Maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) are mucosal α-glucosidases required for the digestion of starch to glucose. We hypothesized that a dietary approach to reduce Mgam and Si activities can reduce glucose generation and absorption, and improve glucose control. Rice starch was entrapped in alginate microspheres to moderate in vitro digestion properties. Three groups of 8-wk old mice (n = 8) were conditioned for 7 d with low 13C-starch-based materials differing in digestion rates (fast, slow, and slower), and then given a digestible 13C-labeled cornstarch test feeding to determine its digestion to glucose. Conditioning of the small intestine with the slowly digestible starches for 7 d reduced jejunal α-glucosidase and sucrase activities, as well as glucose absorption for the slowly digestible starch slower group (P < 0.01). A correlative relationship was found between glucose absorption from a cornstarch test feeding given at d 7 and jejunal α-glucosidase and sucrase activities (R2 = 0.64; 0.67). However, total prandial glucose levels during the 2-h feeding period did not differ. Decreased glucogenesis from a digestible starch feeding was found in mice conditioned on slowly digestible starch diets, suggesting that a dietary approach incorporating slowly digestible starches may change α-glucosidase activities to moderate glucose absorption rate.