AIMS: To evaluate the ability of Candida parapsilosis and Candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from Brazilian red propolis (BZP‐BRP) as compared to fluconazole (FLC). To investigate possible synergy between BZP‐BRP and FLC and anidulafungin (AND). METHODS AND RESULTS: To analyse the development of resistance, isolates susceptible to these antifungals were cultured in increasing concentrations of FLC and BZP‐BRP. The increase in FLC minimum inhibitory concentration for all isolates was evident and the majority developed resistance, whereas none isolated became less susceptible to BZP‐BRP. Synergism was investigated by checkerboard method. BZP‐BRP demonstrated synergy with FLC and indifference with AND for most isolates. CONCLUSIONS: In conclusion, the synergism observed with FLC suggests that BZP‐BRP could be a possible therapeutic strategy for the treatment of infections related to FLC‐resistant Candida sp. SIGNIFICANCE AND IMPACT OF THE STUDY: The indiscriminate use of antifungals results in the emergence of drug‐resistant strains among previously susceptible populations. BZP‐BRP can become an alternative for the treatment of persistent infections caused by Candida sp.