Oral biofilms are a group of healthy synergistic organisms, that on interplay with the immune system undergo transition and colonize the pathogenic bacteria, leading to various diseases like dental caries, gingivitis, periodontitis and a few systemic conditions. Dental caries being the most common disease of the oral cavity, comprise a heterogeneous group of bacteria that can cause imbalance in the biofilm. Caries prevention has been in research for decades, where antibiotics, chemical biocides and fluoride-antimicrobial approaches have not been adequate for this multifactorial disease. In recent years, the major focus of caries prevention has been shifted to plaque-biofilm modification as an ecological approach that would prevent bacterial colonization. Saliva produces various natural antimicrobial peptides that can regulate biofilm modification. Synthetic production of antimicrobial peptides concentrates on selective elimination and a targeted approach towards cariogenic pathogens, precisely Streptococcus mutans (S. mutans). A search in Medline/PubMed, EBSCO and ScienceDirect databases on C16G2, antimicrobial peptides (AMPs) and S. mutans, using MeSH (Medical Subject Heading) terms was performed and papers published until 2020 were included for further evaluation. A total of eight articles written in English with available full texts were selected based on the search strategy. They included four publications on AMPs against S. mutans and another four articles on AMPs in caries prevention. This review focuses on C16G2 antimicrobial peptide and its potential to modify biofilm and inhibit the targeted bacteria causing dental caries.