In this study, we investigated how homoserine-lactone affects the growth and invasion ability of C. auris, a multidrug-resistant fungal pathogen, as well as its in vivo effect in an immunocompromised mouse model. Our findings showed that homoserine-lactone inhibited the growth of C. auris within 4 hours of exposure and increased its invasion ability over time. We also discovered that lower concentrations of homoserine-lactone (50 and 100 μM) effectively reduced kidney tissue fungal burden in immunosuppressed mice, along with corresponding reductions in histopathological lesions, while higher concentrations produced similar results to the control. These results suggest the importance of interspecies communication in microbial interactions and its potential as a therapeutic target. Understanding the communication mechanisms between microorganisms can lead to the development of new strategies for combating infections and reducing reliance on traditional antibiotics. For example, homoserine-lactone could be developed as an antifungal agent for the treatment of infections caused by C. auris or other fungal pathogens.