Background: The reduction of Streptococcus mutans from the oral cavity or its adherence to tooth surfaces can prevent or decrease the progression of caries. In this study, the antimicrobial and anti-adherence properties of Pistacia atlantica ( P. atlantica ) resin (Essential oil [EO] and methanolic extract [ME]) were investigated on S. mutans strains. Materials and Methods: In this in vitro experimental study, the growth rate, biofilm formation ability, and antibiotic susceptibility profile of S. mutans ATCC35668 and 3 strains isolated from caries lesions were studied. The EO and ME of P. atlantica resin were prepared. The anti-bacterial and anti-adherence properties of them were evaluated using microdilution and microplate adherence tests, respectively. The data were statistically analyzed using SPSS with one-way and two-way analysis variance. Direct comparisons between the groups were made using the Wilcoxon W-Mann–Whitney U -test. Statistical significance was set at P < 0.05. Results: All target strains showed the same growth rate and antibiotic susceptibility profile and were found strongly adherent. Both EO and ME showed moderate anti-bacterial properties (growth reduction up to 47.1% and 39.1%, respectively) against S. mutans , while the anti-bacterial effect of EO was higher than ME, significantly ( P < 0.05). In all tested concentrations, EO showed a significantly stronger anti-adherence activity (50%–80%) than ME. Conclusion: The results showed an anti-cariogenic effect of EO extracted from P. Atlantica resin. Considering that S. mutans adhesion is a necessary step in the beginning and progression of dental caries, this study can suggest the use of such extract in mouthwashes or toothpaste as an alternative agent for preventing bacterial attachment and biofilm formation.