Infections caused by bacterial biofilms are an emerging threat to human health. Conventional antibiotic therapies are ineffective against biofilms due to poor penetration of the extracellular polymeric substance secreted by colonized bacteria coupled with the rapidly growing number of antibiotic-resistant strains. Essential oils are promising natural antimicrobial agents; however, poor solubility in biological conditions limits their applications against bacteria in both dispersed (planktonic) and biofilm settings. We report here an oil-in-water cross-linked polymeric nanocomposite (∼250 nm) incorporating carvacrol oil that penetrates and eradicates multidrug-resistant (MDR) biofilms. The therapeutic potential of these materials against challenging wound biofilm infections was demonstrated through specific killing of bacteria in a mammalian cell–biofilm coculture wound model.