We have previously shown that the ethanolic diluted essential oils of the aerial parts of Mentha longifolia could have nitrofurantoin resistance breaker activity against nitrofurantoin resistances Entherobacteriaceae. Bioassay-guided fractions of silica gel thin layer chromatography elute using the nitrofurantoin resistance test strains resulted one compound in active fraction containing a monoterpene piperitone. Piperitone at the concentration of 1 mg/mL decreased MICs of all resistance strains to less than 32 μg/mL. In the presence of piperitone the MICs of nitrofurantoin becomes about 8 times smaller than that of in its absence. Also it is found that in the presence of piperitone the emergence of nitrofurantoin-resistant variants among wild type strains is completely suppressed. Taken together, these results indicate that piperitone could have potential therapeutic effect on nitrofurantoin-resistance chemotherapy.