Oral biofilms are complex three-dimensional structures that develop from a conditioning saliva-derived film, also known as a pellicle, on the tooth surface. This is followed by the attachment of primary microbial colonizers to the host derived receptor molecules present in the acquired pellicle. These early colonizers then promote subsequent interactions with secondary colonizers that join the growing biofilm creating a mature multispecies microbial community. These oral biofilms are known to contribute to some of the most common infectious diseases and are of major public health concern. One component of these biofilms, Streptococcus mutans is considered a principal etiological agent of dental caries. It is known to be involved in the dissolution of tooth enamel by acid release resulting from carbohydrate metabolism. Eradicating or drastically reducing dental biofilm is difficult, and simply brushing the teeth is not always sufficient. One solution to this biofilm buildup is the disruption of the communication system that is used by the biofilm forming microorganisms, a system called quorum sensing (QS). Quorum sensing is a process of chemical communication that bacteria use to orchestrate group behaviors and controls virulence factor production and biofilm formation. In the current study, 3,3′-diindolylmethane demonstrated 73% inhibition of biofilm formation in a static biofilm model of S. mutans. This molecule also showed about 33% or 50% inhibition of biofilm formation in 24 or 48 hours respectively, in flow cell biofilm model of S. mutans. Using such novel anti QS compounds in oral hygiene may play important roles in dental health.