© The author(s) or their institution(s).Saliva is essential for the maintenance of oral health. When salivary flow is impaired, the risk of various oral diseases such as caries and candidiasis increases drastically. Under healthy conditions, saliva provides effective protection against microbial colonization by the collaborative action of numerous host-defense molecules. This review describes how saliva has been the guideline for the design and characterization of a heterodimeric antimicrobial construct called LFchimera. This construct mimics the helical parts of two antimicrobial domains in the crystal structure of bovine lactoferrin. It shows high antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, fungi, and parasites including biowarfare agents such as Bacillus anthracis, Burkholderia pseudomallei, and Yersinia pestis. Further, sublethal concentrations of LFchimera inhibited biofilm formation, the invasiveness of HeLa cells by Yersinia spp., and prevented haemolysis of enteropathogenic Escherichia coli, demonstrating the versatility of these peptides.