Coastal seawater desalination using reverse osmosis (RO) membranes has the potential to alleviate water stress in arid regions. However, membrane biofouling, caused by bacterial biofilm formation, is a significant challenge for seawater desalination plants. Biofilm formation is regulated by quorum sensing (QS) pathways where bacteria secrete auto-inducer molecules to communicate with neighboring bacteria to activate biofilm formation. This research investigated the role of the QS system and the effect of QS inhibiting (QSIs) compounds on marine biofilm production and membrane biofouling. This study revealed that four different marine bacteria isolated from fouled RO membranes in a desalination plant produced two low molecular weight auto-inducer 1 (AI-1) QS molecules. Vanillin and cinnamaldehyde were then identified as the most effective QSI compounds with reduction of marine biofilm formed by RO membrane biofouling isolates and native uncultured seawater bacterial communities by more than 79% and 70%, respectively in a microtiter plate assay. Further investigation into the anti-biofouling capabilities of vanillin and cinnamaldehyde in a cross-flow membrane bio-monitoring system indicated that vanillin in the bulk fluid (1200 mg/L) significantly reduced extracellular polysaccharides (>40%) and dead cells (>20%) on the RO membrane surface. In order to improve the membrane in-situ anti-biofouling potential, vanillin and cinnamaldehyde were physically adsorbed onto various RO membrane surfaces. The addition of the QSI layer on the RO membrane surface significantly altered the membrane surface contact angle along with a less than 16% reduction in pure water permeability, but there was no significant change in salt rejection compared to unmodified membranes. Under biofouling conditions consisting of four mixed marine bacterial species in a high pressure RO system, QSI modified membranes experienced a minimal loss in permeate flux compared to unmodified membranes. Extracellular polysaccharide production, live cells, and dead cells were significantly suppressed on vanillin and cinnamaldehyde modified membrane surfaces by more than 15%, 58%, and 61%, respectively. These findings indicate that QSIs have the potential to suppress marine biofilm formation and membrane biofouling for seawater desalination.