The present study aims to carry out the chemical characterization and microbiological potential of Piper mikanianum essential oil (EOPm), providing data that allows the development of a low‐cost mouthwash formulation aimed at vulnerable communities. The evaluation of the antibacterial activity and modulator of bacterial resistance was performed by the microdilution method to determine the minimum inhibitory concentration (MIC). The chemical components were characterized by gas chromatography coupled to mass spectrometry, identified 28 constituents, in which Safrole Phenylpropanoid is the major compound, representing 72.6% of the total composition, followed by α‐pinene (10.7%), Limonene (2%), β‐caryophyllene (2%), E‐nerolidol (1.9%), spathulenol (1.3%) and camphene (1.1%). The EOPm showed a MIC minimum inhibitory concentration ≥ 1024 µg/mL for all bacterial strains used in the tests. When the EOPm modulating activity combined with chlorhexidine, mouthwash, ampicillin, gentamicin and penicillin G was evaluated against bacterial resistance, the oil showed significant synergistic activity, reducing the MIC of the products tested in combination, in percentage between 20.6% to 98 .4%.