The formation of biofilms on tooth surfaces, called dental plaque, is a prerequisite for the development of both dental caries and periodontal disease. Streptococcus mutans plays an important role in the development of dental caries. Fluoride is routinely used to protect teeth against decay. In the current study, we examined whether we can use a sonochemical based method to coat artificial teeth with MgF2 nanoparticles (NPs). The results showed that the artificial tooth surface was homogenously and evenly covered with an MgF2 NP layer and successful in inhibiting S. mutans biofilm formation by over 60%. This antibiofilm activity was also present following incubation with saliva. The activity was dependent on the nano-crystalline characteristics of the material as fluoride ions could induce a similar reduction in biofilm formation. Taken together, our results indicate that the surface modification of artificial teeth with MgF2 NPs can be effective in preventing the S. mutans biofilm.