The development and spread of pathogenic bacteria that are resistant to the existing catalog of antibiotics is a major public health threat. Biofilms are complex, sessile communities of bacteria embedded in an organic polymer matrix which serve to further enhance antimicrobial resistance. Consequently, novel compounds and innovative methods are urgently required to arrest the proliferation of drug-resistant infections. Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of Nisin on multi drug resistant oral bacteria, isolated from human oral cavities. Chlorhexidine resistant Streptococcus mutans, penicillin resistant Streptococcus sanguinis and Streptococcus gordonii, tetracycline resistant Streptococcus mitis, metronidazole resistant Lactobacillus acidophilus and Actinomyces israelii were isolated from supragingigival biofilms. The minimum inhibitory concentrations and minimum bactericidal concentrations of taxonomically distinct oral bacteria were determined using agar and broth dilution methods. Nisin inhibited planktonic growth of oral bacteria at low concentrations (2.5–50μg/ml). Accordingly, it has been suggested that antimicrobial peptides could be used as novel natural inhibitors that can be used in formulations with synergistically acting antibiotic. This work highlights the potential therapeutic value of food grade nisin to inhibit the growth of oral bacteria and the development of biofims relevant to oral diseases.