The aim of this study was to develop colon-specific delivery systems of ondansetron using natural polymers such as guar gum and sodium alginate. For this purpose colon specific matrix tablets were prepared by a direct compression method. The physical properties of the tablets were tested and in vitro release studies were performed by a flow-through cell apparatus. The amount of polymers affected the in vitro drug release from the matrix tablets. A high amount of polymers provided slow drug release whereas the release of ondansetron from the tablets prepared with low amount of polymers was found to be fast. Ondansetron-alginate and/or guar gum matrix tablet formulations can deliver the drug to the small and large intestine thus these matrix may be a promising system for the reduction of visceral sensitivity and inhibition of motor activity in irritable bowel syndrome (IBS).