The benzoxazoles and benzothiazoles derivatives have a variety of pharmacological activities, such as antimicrobial activity. Thus, in the present study, the antifungal activity of thirteen benzoxazole and benzothiazole derivatives against Candida spp. strains were evaluated. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were established. Compound 1 presented strong antimicrobial action for C. krusei with MIC of 15.6 μg/mL, moderate activity against strains of C. albicans (62.5 μg/mL), and weak activity against C. tropicalis with a MIC value of 125.0 μg/mL. In addition, it was evidenced that biological activity occurs in the plasma membrane in C. albicans. The results of the in silico study showed that the predicted inhibition of HSP90 and aldehyde dehydrogenase could explain the antifungal activity of compound 1. Therefore, the data highlight the potential of these compounds as prototypes in the search for new drugs against Candida species.