AimsThe aim of this study was to investigate the invitro susceptibility of Pythium insidiosum to combinations of the antifungal drugs terbinafine or itraconazole with Melaleuca alternifolia, Mentha piperita and Origanum vulgare essential oils (EOs). Methods and ResultsIn vitro combinations of antifungal drugs with EOs were evaluated by checkerboard microdilution method against 20 Brazilian isolates of P.insidiosum. The tests were performed according to protocol M38-A2, and the interpretation of each combination result was based on the values of the fractional inhibitory concentration index. The combinations of itraconazole with EOs presented prominent synergistic effects against P.insidiosum isolates, and no antagonism was observed with these combinations. However, the combinations of terbinafine with EOs resulted in indifferent or antagonistic effects. ConclusionsThe combination of plant-derived bioactive compounds with antifungal drugs may be an alternative therapy for the control of infections caused by P.insidiosum. Studies of new therapeutic protocols involving these proposed combinations are needed. Significance and Impact of the StudyThe antimicrobial combinations using EOs with terbinafine or itraconazole can be an attractive therapeutic option for controlling P.insidiosum infections.