Plant extracts have been used for millennia for treatment of disease, with much recent interest focusing on the antimicrobial activities of plant essential oils (EOs). Although EOs are active against common microbial pathogens, their effective use as topical, environmental, or food antimicrobials will require EO-based formulations with enhanced antimicrobial activities. In this study, two polyionic compounds, sodium polyphosphate (polyP, a polyanion) and polyethylenimine (PEI, a polycation), were evaluated for their abilities to enhance the antimicrobial activities of six EOs against the human pathogens Escherichia coli O157:H7, Salmonella enterica subsp. enterica ser. Minnesota, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus, and Candida albicans. EOs tested were cinnamon, clove, regular and redistilled oregano, and two types of thyme oil. EOs were examined via disk diffusion and broth microdilution, either alone or in the presence of subinhibitory levels of polyP or PEI. Both polyP and PEI were found to be effective enhancers of EO activity against all strains examined, and calculation of fractional inhibitory indices for select EO/organism pairings demonstrated that true synergy was possible with this enhancement approach. Experiments with a deep-rough strain of S. Minnesota probed the role of the outer membrane in both intrinsic resistance to EOs and enhancement by polyions. The use of polyP and PEI for boosting the antimicrobial activities of EOs may eventually facilitate the development of more effective EO-based antimicrobial treatments for use in applications such as wound treatment, surface disinfection, or as generally recognized as safe antimicrobials for use in foods or on food contact surfaces.