The peroral administration of peptide drugs is a major challenge to pharmaceutical science. In order to provide a sufficient bioavailability of these therapeutic agents after oral dosing, several barriers encountered with the gastrointestinal (GI) tract have to be overcome by a suitable galenic. One of these barriers is caused by proteolytic enzymes, leading to a severe presystemic degradation in the GI tract. Besides some other strategies to overcome the so-called enzymatic barrier, the use of inhibitory agents has gained considerable scientific interest, as various in vivo studies could demonstrate a significantly improved bioavailability of therapeutic peptides and proteins, due to the co-administration of such excipients. In vitro techniques to evaluate the actual potential of inhibitory agents incubation with pure proteases, freshly collected gastric or intestinal fluids, mucosal homogenates, brush border vesicles and freshly excised mucosa. In situ techniques are based on single-pass perfusion studies cannulating different intestinal segments and determining the amount of undegraded model drug in perfusion solutions or blood. For in vivo studies, insulin is mostly used as a model drug, offering the advantage of a well-established method to evaluate the biological response after oral dosing by determining the decrease in blood glucose level. Generally, inhibitory agents can be divided into: inhibitors which are not based on amino acids (I), such as p-aminobenzamidine, FK-448 and camostat mesilate; amino acids and modified amino acids (II), such acid derivatives; peptides and modified peptides (III), e.g. bacitracin, antipain, chymostatin and amastatin; and polypeptide protease inhibitors (IV), e.g. aprotinin, Bowman-Birk inhibitor and soybean trypsin inhibitor. Furthermore, complexing agents and some mucoadhesive polymers also display enzyme inhibitory activity. Drawbacks of inhibitory agents, such the risk of toxic side effects or high production costs, might be excluded by the development of advanced drug delivery systems. Initial steps in this direction can be seen in the development of delivery system containing mucoadhesive polymers providing an intimate contact to the mucosa, thereby reducing the drug degradation between delivery system and absorbing membrane, controlled release systems which provide a simultaneous release of drug and inhibitor and in the immobilisation of enzyme inhibitors on delivery systems.