Poly(gamma-glutamic acid)s (gamma-PGA) modified with phloridzin, which is an inhibitor of the Na(+)/glucose cotransporter (SGLT1), via a omega-amino triethylene glycol linker were synthesized. The potential of gamma-PGA-phloridzin conjugates (PGA-PRZs) obtained as a novel oral anti-diabetic drug was examined by in vitro and in vivo experiments. A PGA-PRZ with a 15% phloridzin content inhibited glucose transport from mucosal to serosal sides of the everted rat's small intestine, and its inhibitory effect was as strong as that of intact phloridzin. When the PGA-PRZ was given orally to rats before glucose administration, the glucose-induced hyperglycemic effect was significantly suppressed. On the other hand, reduction of an increase in the blood glucose concentration was scarcely observed when the PGA-PRZ was substituted with a double amount of intact phloridzin. This difference in the biological activity between PGA-PRZ and intact phloridzin might have resulted from the improved stability of a glucoside bond of phloridzin through the conjugation with gamma-PGA. These results suggest that the gamma-PGA-phloridzin conjugates have potential as oral anti-diabetic drugs.