Aim: Phytomedicine has been commonly practiced as a form of traditional medicine in various cultures for the treatment of oral diseases. Recently, it has gained importance as an alternative to conventional treatment. Several extracts of plants and fruits have been recently evaluated for their potential activity against microorganisms involved in the development of dental caries. The purpose of this study was to evaluate the antimicrobial activity and antiadherent effect of the crude organic extract (COE) and three partitions (aqueous, butanolic, and chloroformic) of Psidium guajava (guava) leaves on a cariogenic biofilm model. Materials and methods: Guava leaves were obtained from the mountains of northern Peru, where they grow wild and free of pesticides. The antimicrobial activity of the COEs and partitions against Streptococcus mutans and Streptococcus gordonii was determined by measuring the inhibition halos, while the effect on biofilm adhesion was determined by measuring the optical density using spectrophotometry. Results: An antibacterial effect of the COE and chloroformic partition against S. gordonii (p < 0.05) was found, as was a significant effect on biofilm adherence, with a minimum inhibitory concentration (MIC) of 0.78 mg/mL, which was maintained throughout the 7 days of evaluation. Conclusion: We conclude that the COEs and their chloroformic partition have antimicrobial and antibiotic effects against this strain of S. gordonii, making them of particular interest for evaluation as a promising alternative for the prevention of dental caries. Clinical significance: By knowing the antimicrobial effect of Psidium guajava, this substance can be effectively used in products aimed to prevent dental caries and periodontal disease.