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Resistance to antifungal therapy of <i>Candida albicans</i> and non-<i>albicans Candida</i> strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against <i>Candida</i> species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of <i>C</i>. <i>albicans</i>, <i>C. tropicalis</i> and <i>C. glabrata</i> was the <i>D</i>-isomer of Cateslytin (<i>D</i>-bCtl) whereas the efficiency of the <i>L</i>-isomer (<i>L</i>-bCtl) significantly decreases against <i>C. glabrata</i> strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the <i>L</i>-bCtl and <i>D</i>-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the <i>L</i>- isomer of Catestatin (<i>L</i>-bCts) had a synergistic effect against <i>Candida albicans</i> especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with <i>L</i>-bCtl, suggesting the importance of the C-terminal end of <i>L</i>-bCts (GPGLQL) for the interaction with BSA. In this context in vitro <i>D</i>-bCtl, as well as the combination of BSA with <i>L</i>-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to <i>Candida</i> and non-<i>Candida albicans</i>, without detrimental side effects.