Antimicrobial peptides (AMPs) are key to defence against infection in plants and animals. Use of AMP mutations in Drosophila has now revealed that AMPs can additively or synergistically contribute to defence in vivo. However, these studies also revealed high specificity, wherein just one AMP contributes an outsized role in combatting a specific pathogen. Here, we show the Drosocin locus (CG10816) is more complex than previously described. In addition to its namesake peptide 'Drosocin', it encodes a second mature peptide from a precursor via furin cleavage. This peptide corresponds to the previously uncharacterized 'Immune-induced Molecule 7'. A polymorphism (Thr52Ala) in the Drosocin precursor protein previously masked the identification of this peptide, which we name 'Buletin'. Using mutations differently affecting Drosocin and Buletin, we show that only Drosocin contributes to Drosocin gene-mediated defence against Enterobacter cloacae. Strikingly, we observed that Buletin, but not Drosocin, contributes to the Drosocin gene-mediated defence against Providencia burhodogranariea, including an importance of the Thr52Ala polymorphism for survival. Our study reveals that the Drosocin gene encodes two prominent host defence peptides with different specificity against distinct pathogens. This finding emphasizes the complexity of the Drosophila humoral response and demonstrates how natural polymorphisms can affect host susceptibility.