Aims: The aim of this study was to attempt to evaluate the antifungal activity of carvacrol in combination with fluconazole or amphotericin B against Candida albicans. Methodology and results: Antifungal susceptibilities to carvacrol alone and in combination with fluconazole or amphotericin B were performed using the CLSI standard reference method against clinical isolates of C. albicans isolated from the immuno-compromised patients. Proteinase production assay and the expression of genes associated with secreted aspartyl proteinases synthesis (SAP1 and SAP2) were carried out to evaluate the antifungal activity of carvacrol in combination with fluconazole or amphotericin B against C. albicans. The carvacrol alone and in combination with fluconazole and amphotericin B exhibited strong inhibitory activity. The carvacrol, exhibited significant synergy and bpartial synergy with fluconazole or amphotericin B against the test isolates. The data indicated that combination of carvacrol with fluconazole or amphotericin B exerted antifungal effects through reducing SAP enzyme activity. The expression levels of SAP1 and SAP2 genes were down-regulated by carvacrol, fluconazole and amphotericin B alone. After carvacrol was employed in combination with fluconazole or amphotericin B, the expression levels of SAP1 and SAP2 genes demonstrated the lower expression in comparison to carvacrol alone. Conclusion, significance and impact of study These results provide proof of concept for the implementation of carvacrol alone or in combination with fluconazole or amphotericin B inhibitors of C. albicans.