We determined the inhibitory activity of the essential oil fraction obtained by steam distillation from the fresh and dried leaves of Perilla frutescens var. acuta against some pathogenic Salmonella and Vibrio spp. The activities of compounds isolated from the essential oils, apiol and myristicin, were also tested and the results were compared with those of the essential oil fraction. The Perilla essential oil fraction and its main components showed significant inhibition against antibiotic-susceptive and antibiotic-resistant strains of the tested Salmonella and Vibrio strains. Synergistic or additive effects were identified by combing the oils with ampicillin by checkerboard-titer tests. We conclude that essential oils from P. frutescens can be useful in the treatment of Salmonella and Vibrio infections and as safe additives to food materials for the prevention of contamination of food by these bacteria. This is especially important because of the rapid increase in antibiotic-resistant strains, which could cause severe symptoms in humans.