It has been previously described that antibiotic-resistant bacteria can be found in the guts of insects feeding on a variety of plants and not exposed to significant levels of antibiotics. Such naturally-occurring resistance has implications for clinically-relevant antibiotic resistance, which is a worldwide problem, and for using plants as a source of potential novel antibiotics. We investigated this phenomenon further. Firstly, we searched for antibiotic resistance in different insects’ guts and explored its origin, using two Lepidopteran hosts feeding on artificial food containing either ciprofloxacin or oxytetracycline. We discovered that these antibiotics have a diverse impact on the insect gut microbiome, beyond simply inducing antibiotic resistance. Secondly, we used the insect gut bacteria to identify plant extracts with antibacterial activity, and purified their active fractions. We found that vindoline, from leaf extract, and serpentine, from root extract, are the most abundant metabolites in active fractions of Madagascar periwinkle extracts. Finally, we developed one of the insect species we used, Galleria mellonella, into a laboratory model for antibiotic efficacy testing, toxicity testing and as a model for human baby gut. In summary, in this project we explored different aspects of the antibiotic resistance that can be found in the insect gut and used it to guide us towards plant metabolites with antibacterial properties.