<p>Background: <em>Staphylococcus aureus (S. aureus)</em> causing numerous diseases in humans, have become resistant to antibiotics, hence, urging the need for alternative medicines.&nbsp;<br /> Methods: In this study, the Indian medicinal weed, <em>Ruellia patula (R. patula)</em> extracted and fractioned through column chromatography was subjected to antibacterial and anti-quorum sensing activity against <em>S. aureus</em> and Methicillin Resistant Staphylococcus aureus MRSA.<br /> Results: The obtained results confirmed fraction F44 to have significant effect as antimicrobial and anti-biofilm agent against both the micro-organism. Therefore, few of such highly active fractions were chemical finger printed using GC-MS and the compounds identified were further docked with DNA binding (LytTR) domain of agrA, which revealed that compounds identified from fraction were interactive to the protein.<br /> Conclusion: <em>R. patula</em> is promising antimicrobial and anti-biofilm agent against S. aureus and MRSA.</p>