The increase in the occurrence of the multidrug-resistant bacteria is the cause of need in the discovering new antimicrobial substances and antimicrobial combination drugs. The aim of this study was to investigate the synergistic interaction between polar fractions of pomegranate (Punica granatum L.) peel and Amoxicillin trihydrate against Enterococcus faecalis. In the first step of the study, polar fractions of pomegranate peel (ethyl acetate, butanol, distilled water) were prepared. Next, disc diffusion method was used for determination of the synergic effect.Here, the results indicated that the mixture of prepared polar fractions of pomegranate peel and Amoxicillin trihydrate showed synergistic interaction against E. faecalis. This study determined that polar fractions of pomegranate peel (ethyl acetate, butanol, distilled water) improved the effectiveness of Amoxicillin trihydrate against E. faecalis. Pomegranate peel may have potential applications in the new antibacterial therapy combinations due to its easy accessibility, therapeutic properties and being low cost. Results of the present study may be beneficial for further studies about the characterization of phytochemical compounds that are responsible for the improvement of the antibiotic effectiveness.