Streptococcus mutans is the leading one of the oral microbiota causing tooth caries. It forms biofilms on teeth providing protection against the host defenses by making extracellular polysaccharides and carbohydrates. These biofilms increase bacterial persistence and enhances the pathogenicity of S. mutans. Such emergence of antibiotic resistance has significantly reduced the long-term usage of both synthetic and conventional antimicrobials (β lactams and chlorhexidine). The need to find and develop novel alternatives is owing to this growing resistance. Natural antimicrobials, like enzyme-based medications and other antimicrobial peptides (AMPs), provide good treatments. AMPs also minimize the chance of developing resistance and disrupts bacterial membranes preventing the formation of biofilms. By directly breaking down biofilm matrix and virulence factors, enzyme-based antimicrobials such glucosidases and proteases improve bacterial clearance. Both strategies are viable substitutes for conventional antibiotics since they are biocompatible, environmentally benign, and have several targets of action. The relevance of switching to natural antimicrobial drugs is shown by the collective research on S. mutans prevalence, biofilm biology, and resistance mechanisms. Incorporating AMPs and enzyme-based treatments into oral healthcare may offer safe, efficient, and resistance-reducing methods for managing and preventing dental caries.