Dental caries is considered to be one of the most prevalent infectious disease in humans across all age groups because they affect 60-90% of the world’s population. With the introduction of refined sugar into the modern diet and an improved understanding of the pathogenesis of dental caries, the need for novel approaches to caries prevention has become is a key undertaking for addressing the caries burden in the 21st century. While previous studies have shown successful elimination of bacteria in the oral cavity, only a few modalities such as antimicrobial peptides, vaccines and more recently, nanoparticles, have been developed to specifically target Streptococcus Mutans. Here, we discuss the significance of the biofilm and the essential role of Strep. mutans in the development of dental caries. We focus on current and prospective therapeutic approaches against dental caries, including chemical modalities such as fluoride and chlorhexidine, vaccines, antimicrobial peptides, replacement therapy, quorum sensing targets, nanoparticles and natural products. Further research is needed to develop a safe and efficacious approach against caries, or specifically Streptococcus Mutans, in humans