Aims: This study aimed to evaluate the efficacy of 'natural' putative antimicrobial agents against Streptococcus mutans and to compare these with synthetic agents using the flow microcalorimeter. Streptococcus mutans is one of the oral pathogens responsible for dental caries. Methods and Results: Traditional microbiological techniques are invasive and destructive unlike flow microcalorimetry. This rapid technique was used to continuously monitor the power output (bioactivity) of Strep. mutans with reproducibility, precision and accuracy. The antibacterial agents found in oral hygiene products and all the natural agents tested showed anti-Strep. mutans ability. Conclusions: In this study microcalorimetry; identified agents that had a biological effect and quantified the rate of kill achieved enabling four broad categories of antimicrobial agent to be defined. Significance and Impact of the Study: Microcalorimetric data are a better indication of antimicrobial efficacy than merely determining concentrations at which an antimicrobial agent is bacteriostatic or bactericidal.