The human peptide LL-37 can kill the drug‑resistant fungus Candida auris in lab tests, especially when mixed with existing antifungal drugs, by breaking its cell membrane and stressing its cells. However, these results are only from test‑tube experiments, not human trials, so they don’t yet translate into a safe DIY treatment.

<i>Candida auris,</i> an evolving multidrug-resistant pathogenic yeast, is known for causing severe invasive infections associated with high mortality rates in hospitalized individuals. Distinct from other <i>Candida</i> species, <i>C. auris</i> can persist for longer periods on different surfaces and is resistant to all of the major classes of antifungal drugs. Therefore, there is an urgent need for new antimycotic drugs with improved efficacy and reduced toxicity. The development of new antifungals based on antimicrobial peptides from various sources is considered a promising alternative. In this study, we examined the in vitro anti-yeast activity of the human cathelicidin peptides LL-37 against clinical strains of <i>C. auris</i> alone and in combination with different antifungal drugs by broth microdilution assay. To understand the antifungal mechanism of action, cell envelopes, cell cycle arrest, and effect on oxidative stress enzymes were studied using standard protocols. The minimum inhibitory and fungicidal concentrations of cathelicidin LL-37 ranged from 25-100 and 50-200 &#xb5;g/mL, respectively. A combination interaction in a 1:1 ratio (cathelicidin LL-37: antifungal drug) resulted in 70% synergy with fluconazole and 100% synergy with amphotericin B and caspofungin. Assessment of the <i>C. auris</i> membrane by using propidium iodide assay after exposure to cathelicidin LL-37 linked membrane permeabilization with inhibition of <i>C. auris</i> cell growth and viability. These results were backed up by scanning electron microscopy studies demonstrating that exposure with cathelicidin LL-37 caused <i>C. auris</i> cells to undergo extensive surface changes. Spectrophotometric analysis revealed that cathelicidin LL-37 caused oxidative stress in <i>C. auris,</i> as is evident from the significant increase in the activity of primary antioxidant enzymes. In addition, cathelicidin LL-37 inhibited the cell cycle and accumulated cells in the S phase. Therefore, these results specify the potential of cathelicidin LL-37 for developing a new and effective anti-<i>Candida</i> agent.