Introduction: Meniran (Phyllanthus niruri, L.) contains alkaloid that are antibacterial. Synergistic effect were found in fractions that were thought to contain alkaloids and other compounds with amoxicillin and chloramphenicol antibiotics agains Staphylococcus aureus bacteria. However, the combination of pure alkaloids Phyllanthus niruri, L. with antibiotics in inhibiting Staphylococcus aureus bacteria not been proven. So this study aims are examine the interaction of the alkaloid Phyllanthus niruri, L. with amoxicillin or chloramphenicol against Staphylococcus aureus. Methods: This study used in vitro experimental methods that is colony of Staphylococcus aureus is gram positive . The extraction and isolation of the alkaloid Phyllanthus niruri, L. using methods maceration with chloroform, soxhletation with methanol, re-extraction with dichloromethane and finally fractionation. The extraction result were tested with phytochemical to ensure the success of extraction. Determination of the Zone of Inhibition (ZOI) that is clear zone around the disc against Staphylococcus aureus by Kirby-Bauer method and the interaction test was assessed based on the AZDAST method. Results: The results of the phytochemical test showed the alkaloid compound Phyllanthus niruri, L of fractions 1-3. The mean ZOI combination of Phyllanthus niruri, L. alkaloid fraction 2 (18,35 mm ± 2,33 mm) & fraction 3 (18,35 mm ± 2,33 mm) with amoxicillin antibiotics was higher than single antibiotics (17,72 mm ± 3,79 mm), but at fraction 1 (15,86 mm ± 1,97 mm) it was lower and it was suspected of having antagonistic interactions. Meanwhile, the mean ZOI combination of Phyllanthus niruri, L. alkaloid fraction 1 (27,90 mm ± 1,30 mm) with chloramphenicol antibiotics was higher than single antibiotics (27,44 mm ± 0,94 mm) and in fraction 2 (25,97 mm ± 0,44 mm) & fraction 3 (27,21 mm ± 0,96 mm) were lower than single antibiotics (27,44 mm ± 0,94 mm) so it was suspected of having antagonistic interactions. The result of interaction types in combination fraction are not distinguishable (ND). Conclusion: A single fraction of the alkaloid compound Phyllanthus niruri, L. with amoxicillin or chloramphenicol against Staphylococcus aureus bacteria not show any inhibitory, while the combination test of fractions 1-3 showed inhibition but not significant. The interaction types in combination fraction are not distinguishable (ND). Keywords : alkaloids of Phyllanthus niruri, L., amoxicillin, chloramphenicol, Staphylococcus aureus bacteria