A series of monocyclic glycoamidines bearing different exocyclic amine, alcohol, or alkyl functionalities and bicyclic amidines derived from D-glucose and D-mannose were synthesized and tested as inhibitors of various glycosidases. All the prepared compounds demonstrated good to excellent inhibition toward glycosidases. In particular, the biscationic D-mannoamidine 9b bearing an exocyclic ethylamine moiety proved to be a selective competitive inhibitor of alpha- and beta-mannosidases (K-i = 6 nM) making it the most potent inhibitor of these glycosiclases reported to date. A favorable B-2,B-5 boat conformation might explain the selectivity of mannosidase inhibition compared to other glycosiclases.