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<i>Candida albicans</i> (<i>C. albicans</i>) is one of the most common fungi in the human body; it is an opportunistic pathogen and can cause candidiasis. Extracellular vesicles (EVs) derived from the host cells have a potentially protective effect against pathogens and can be developed as vaccine formulations. GW4869 can inhibit the production and release of EVs. Previous studies have indicated that GW4869 can alter the immune and inflammatory responses of the host. However, the effect of GW4869 on <i>Candida</i> infection and the anti-<i>Candida</i> response of the host has not been investigated. We evaluated the effect of GW4869 on <i>C. albicans</i> invasion, biofilm formation, and cellular damage in a murine model of oral candidiasis. In this study, <i>C. albicans</i>-infected mice were injected with or without GW4869. The results proven by macroscopic, microscopic, and ultramicroscopic methods showed that GW4869 treatment exacerbated the oral candidiasis of mice, promoted <i>C. albicans</i> invasion and biofilm formation, and aggravated oral mucosal inflammation and cellular ultrastructural damage. The results are beneficial in the further exploration of the immune mechanism of <i>C. albicans</i> infection.