The human pathogenic protozoan parasites Entamoeba histolytica and Giardia lambia, triggers of intestinal disturbances mainly in developing countries, are equipped with a set of multiple cysteine peptidases used as weapons to attack their victims. Exertion and control of these enzyme activities are absolutely necessary for the survival of these parasites in their inhospitable environments. Generally, peptidase inhibitors are a common tool of many uni- and multi-cellular organisms to regulate endogenous and exogenous peptidase activities. For the regulation of cysteine peptidase activities, either one of two types of proteinacious inhibitors is frequently used: those of the cystatin and those of the chagasin family. Both types of inhibitors, also appearing as multicopy forms, are relatively small and very resistant proteins widespread in nature. Trophozoites of the protists E. histolytica and G. lamblia also feature these types of specific cysteine peptidase inhibitors, out of which E. histolytica is solely equipped with two chagasin-like proteins, whereas G. lamblia only contains cystatins, both as single copy forms. Another type of proteinaceous peptidase inhibitors is represented by the group of serpins, usually directed against serine peptidases with particular substrate specificities, but in exceptional cases are also able to inhibit cysteine peptidases. Both protozoan parasites each are equipped with single serpin genes, whose physiological targets have not yet been identified. The significance of these findings is discussed.