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The development of new antimicrobial drugs is essential as the human population continues to build resistance to current treatments. Peptidomimetic compounds, those synthesized to mimic the behavior of naturally occurring biological proteins, have demonstrated promise in this area. Using bicyclic aziridine ring opening reactions, a library of N-acyl aziridinyl peptide isosteres has been synthesized and submitted to biological assays for cysteine protease inhibition, a common pathway to suppression of bacteria. Most of the compounds tested showed good activity against cathepsin B. This research required a novel synthetic approach to selectively generating oxazolidinones and aziridinyl ureas from fused bicyclic aziridines, which was accomplished with solvent selection, nucleophilic amine stoichiometry, and aziridine substitution. To extend the peptidic nature of these compounds, some success was achieved with acylation and amide coupling reactions. A practical approach to generating enantiomerically pure bicyclic aziridines was investigated, however the best enantioselective conditions provided only a 3 : 1 ratio. This stereoselective approach coupled with the ability to incorporate aziridines into peptide chains would ultimately lend a very powerful synthetic strategy for generating libraries of peptidomimetics with broad application potential.