The peptide bonds formed by D-amino acids are more resistant to proteases than those formed by L-amino acids. For example, the amino-terminal Tyr-D-Ala sequence of a peptide drug is not hydrolyzed by aminopeptidases, whereas the corresponding L-peptide is degraded rapidly. Peptides can be modified using D-amino acids to ensure that they are stable against proteolysis, yet retain the same binding properties as their original all-L counterparts. Studies were performed to assess the antigenic properties and enzymatic stability of several MUC2 peptides whose residues were replaced with D-amino acids in the flanking regions.

Racemase is an enzyme used by cholera bacteria to synthesize large amounts of D-methionine and D-leucine from their L-amino acid counterparts. These D-amino acids instruct cell wall-building proteins to reduce their production of peptidoglycans. The peptide isomerization reaction probably proceeds via deprotonation and reprotonation at the alpha-carbon. This reaction mechanism has been established for the racemases of several amino acids such as those of proline, aspartic acid, and glutamic acid, and two active-site cysteines are involved in this reaction. Racemases are located in the periplasmic space of a bacterium between the inner and outer membranes; it begins synthesizing D-amino acids once the cell stops growing.

Retro-inverso peptides are composed of D-amino acids that are assembled in the reverse order of their parental L-sequences. Retro-inverso peptides are obtained by replacing the normal L-amino acid residues with the corresponding D-amino acids and reversing the direction of the peptide backbone. Therefore, the original spatial orientation and the chirality of the side chains is unchanged. This results in a non-complementary side chain topochemistry between the analog and the parental L-peptide.