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Background: Candidiasis is the common name for diseases caused by yeast of the genus Candida . Candida albicans is one of the most implicated species in superficial and invasive candidiasis. Antifungals, polyenes, and azoles have been used to treat candidiasis. However, due to the development of antifungal resistance, research of natural substances with potential antifungal effects at low concentrations or combined is also a possibility., Methods: The broth microdilution method was used to evaluate the antifungal activity. The biofilm formation was assessed using the microtiter plate method. The antibiofilm activities were assessed using micro plaque tetrazolium salt assay (MTT). The combination effect of antifungal with natural substances was made using the checkerboard method., Results: Among our isolates, clotrimazole was the most resistant, but amphotericin B was the most effective antifungal. The biofilm was formed by all isolates of C. albicans . Curcumin and piperine displayed antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) and minimum eradicating concentration (MBEC) ranging from 64 to 1024  μ g/mL and 256 to 2048  μ g/mL. In combination, piperine presented double synergistic effects compared to curcumin with all antifungals tested. Curcumin shows more synergistic effect when combined with polyenes than with azoles. However, piperine shows a more synergistic effect when combined with azoles compared to polyenes., Conclusion: C. albicans was susceptible to curcumin and piperine both on planktonic cells and biofilm. The combination of curcumin and piperine with antifungals has shown synergistic effects against multiresistant clinical isolates of Candida albicans representing an alternative drug research for the treatment of clinical candidiasis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ulrich Joël Tsopmene et al.)