Cutaneous candidiasis is characterized by an overgrowth ofCandidaleading to skin inflammation and infection. Similar to bacteria,Candidacan develop tolerance to common antifungal drugs. Cold atmospheric plasma (CAP), with its proven antimicrobial properties, offers a promising alternative to the prevailing methods. Because of plasma heterogeneity each new device must be tested individually for its effectiveness. Antimicrobial activity is usually studied using planktonic microorganisms or animal models, making it difficult to extrapolate the results to the human system. Therefore, a 3D skin model of cutaneous candidiasis for the antimicrobial testing of CAP was established. First, the reaction of the 3D-skin model toCandidainfection was examined using various histological and molecular–biological methods. Infection withC. albicansresulted in increased expression and secretion of pro-inflammatory cytokines and augmented expression of antimicrobial peptides. Within 48 h, hyphal growth spread throughout the model and caused tissue damage. Second, the CAP treatment was employed. It was shown that CAP significantly reduced the spread of the yeast in the infected skin models as well as decreased the expression and secretion of the infection markers. The plasma device exhibited a high antifungal activity by completely inhibiting hyphal growth and reducing inflammation at the highest treatment duration.