The inhibitory activity of N-substituted derivatives of moranoline (1-deoxynojirimycin) against intestinal α-glucosidase and postprandial hyperglycemia was evaluated. None of the N-substituted derivatives studied displayed more potent inhibition of sucrase or maltase from rabbit intestines than the parent compound moranoline. However, unlike the in vitro results, many compounds exhibited more potent hypoglycemic activities than moranoline in sucrose-, or starch-loaded rat models. Alkenyl or aralkenyl derivatives displayed more potent hypoglycemic activities than alkyl or aralkyl derivatives. There was a weak correlation between in vitro and in vivo assay systems found by statistical analysis. It is necessary to evaluate compounds in vivo in order to select the most potent hypoglycemic compound.