Glycyrrhizin is a phytocompound which is derived from Glycyrrhiza glabra. It is used in treating the upper respiratory tract disease like cough, bronchitis, laryngitis, sore throat, etc. It has various medicinal uses in rheumatism, peptic ulcers, asthma, allergies, and inflammation. Glycyrrhizin has been reported to possess antibacterial, antiviral, antioxidant, anti inflammatory properties. In view of the above facts, the present in silico study was designed to demonstrate the molecular mechanism underlying the antimicrobial activity of glycyrrhizin against common dental pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Treponema denticola, Enterococcus faecalis and Tannerella forsythia. The STITCH tool was used to identify the drug-protein interaction. The functional class of the protein was deduced using VICMPred, followed by the identification of epitopes on the virulence factors using BepiPred. Further, the subcellular location of the virulence factors were also studied using PSORTb software. The computational analysis performed identified several virulence factors viz., short chain dehydrogenase/reductase family oxidoreductase of Treponema denticola and D-mannonate oxidoreductase of Tannerella forsythia which were found to interact with glycyrrhizin. Interestingly, phosphopyruvate hydratase was found to be the protein present in all the five genera was shown to interact with glycyrrhizin. Thus the present study reveals the target proteins on the dental pathogens which were shown to interact with glycyrrhizin. Furthermore, experimental validation of the results are warranted to provide substantial details on the anti-microbial activity of glycyrrhizin against common dental pathogens.