Slime deposition on paper is a major problem confronted in paper-mills resulting in spoiled quality of the final product and huge economic losses. Conventional methods use chemical biocides for slime eradication which lead to effluent toxicity. Eco-friendly compounds can be used as alternatives for inhibition of biofilm/slime formation by bacteria. Autoinducer-2 (AI-2) based quorum sensing (QS) is a universal communication mechanism present in bacteria. In this study, bacteria isolated from paper-mill slime samples were identified for biofilm forming potential and AI-2 activity. Natural and synthetic compounds from PubChem library were selected by docking with AI-2 producer-LuxS, and were tested for inhibition of biofilm formation by the consortium of all paper-mill bacterial isolates. Triclosan was found to be the best as it reduced the expression of luxS and inhibited biofilm formation, as shown by Field Emission Scanning Electron Microscope (FE-SEM), to 50% at a concentration of 23.43 μg/ml and acted as biocide at 30 μg/ml for complete inhibition of growth when tested in the Research and development (R and D) set-up of paper mill. The pleiotropic inhibition of bacterial communities in paper mills by triclosan at environmentally safe concentrations can therefore stop slime formation and paper deterioration in an eco-friendly way and can prevent economic losses.