Non-ribosomal peptide antibiotics, including polymyxin, vancomycin, and teixobactin, most of which contain D-amino acids, are highly effective against multidrug-resistant bacteria. However, overusing antibiotics while ignoring the risk of resistance arising has inexorably led to widespread emergence of resistant bacteria. Elucidating the little known mechanisms of resistance to peptide antibiotics is critical when implementing peptide antibiotics and would improve effectively improve efficiency.