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Objective: To evaluate the anti Candida activity of Hyptis martiusii decoction and its major compound, caffeic acid alone or in the presence of fluconazole, as well as their cytotoxic effect. Methods: The decoction was characterized using high performance liquid chromatography coupled with diode array detector. For the antifungal activity, the minimum inhibitory concentration (MIC) and the potential effect of the decoction with the fluconazole were evaluated by microdilution method using 96-well microtiter trays. The osmotic fragility test was performed using erythrocytes under saline stress. All tests were performed in triplicate. Results: The chemical characterization of the decoction was performed by high performance liquid chromatography and revealed the presence of seven compounds, including caffeic acid as major constituent. The antifungal tests demonstrated that both decoction (DHm) and caffeic acid obtained from Hyptis martiusii presented MIC and MFC ≥ 4096 μg/mL against Candidaalbicans and Candida tropicalis strains. However, in the presence of fluconazole, DHm and caffeic acid presented IC50 of 2.60 and 2.53 μg/mL respectively, demonstrating significant synergistic effects against Candida strains. The modulator activity of DHm might be due to the presence of caffeic acid. Moreover, DHm and caffeic acid did not cause significant hemolytic effects, indicating that they present low cytotoxicity. Conclusions: These data indicate that DHm potentiates the activity of the fluconazole, without enhancement of the toxicity, encouraging further toxicological, pharmacological and phytochemical studies to provide consistent evidence of the potential of this plant to be used in drug development.