A multitude of microorganisms coexist in the human oral cavity and form polymicrobial biofilms, but the role of microbial interactions in pathogenesis and virulence has remained elusive. This study investigated inter-kingdom communication between the fungal pathogen Candida albicans and the caries-promoting bacterium Streptococcus mutans. Biofilm biomass and cell densities were increased in co-cultures compared with monocultures, whereas the secretion of extracellular polymeric substances that contribute to cariogenesis by S. mutans was inhibited. By contrast, co-culturing with C. albicans led to the induction of quorum sensing in S. mutans, including the expression of genes that are important for survival and competence. Virulent hyphal growth of C. albicans was also promoted, which suggests that both pathogens benefit from inter-kingdom interactions.