A full characterization of proteolytic stability is critical for the successful application of fluorinated peptide based pharmaceuticals. To investigate the impact of fluoroalkyl substitution on the protease resistance of peptides, a small model peptide library was synthesized in which Abu, DfeGly, and TfeGly are incorporated at different guest positions. When subjected to proteolysis, these model peptides allow for a systematic comparison of the substitution effects with respect to the kind of amino acid as well as its position relative to the enzymatic cleavage site (Asante, Bioorg. Med. Chem., 2013). In general, the impact of side chain fluorination on the stability towards α-chymotrypsin and pepsin digestion appears to be a complex phenomenon which depends not only on the position but also on the stiochiometry of fluorination, as well as on the interactions with the enzyme subsites.