BACKGROUND: The consumption of unpasteurized fruit juices poses a food safety risk due to the survival of pathogens such as Enteritidis and O157:H7. METHODS: This study evaluated natural antimicrobials (nisin, coumaric acid, citral, sinapic acid, and vanillin) in orange juice as a strategy to ensure the control of these pathogens during the preservation of the non-thermally treated juices. RESULTS: The addition of nisin, coumaric, or citral did not alter the juice's physicochemical characteristics, ensuring product quality. Nisin (1-2 mL/L), coumaric acid (0.25-0.5 g/L), and citral (0.25-0.5 mL/L) were the most effective in reducing bacterial populations. The antimicrobial activity of the most effective compounds was then tested against both acid-adapted and non-acid-adapted bacteria in refrigerated juice, applying Weibull and linear decay models to assess bacterial inactivation. Non-acid-adapted Enteritidis showed a rapid 5 log reduction after 30 h of refrigeration with the highest nisin dose, while the acid-adapted strain exhibited a smaller reduction (2 and 1.5 log units for 1 and 2 mL/L, respectively). Citral was effective but excluded due to solubility and aroma concerns. Non-acid-adapted O157:H7 showed a 5 log reduction with coumaric acid at 0.5 g/L, whereas acid-adapted strains exhibited a lower reduction (around 1.5 log units). Nisin and coumaric acid also reduced bacterial survival in gastrointestinal tract simulations. However, acid-adapted bacteria were more resistant. CONCLUSIONS: These findings highlight the potential of these antimicrobials for food safety applications, though further studies should explore their mechanisms and combinations for enhanced efficacy.