Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides’ mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.