LL-37, cleaved from human cathelicidin, and human neutrophil peptide-1 (HNP1) from the defensin family are antimicrobial peptides that are occasionally co-released from neutrophils, which synergistically kill bacteria. We report that this couple presents another type of cooperativity against host eukaryotic cells, in which they antagonistically minimize cytotoxicity by protecting membranes from lysis. Our results describe the potential of the LL-37/HNP1 cooperativity that switches from membrane-destructive to membrane-protective functions, depending on whether the target is an enemy or a host.