Invasive fungal infections caused by Candida and Cryptococcus species lead to life threating infections in immunocompromised individuals. Furthermore, increasing incidence of fungal strains resistant to FDA-approved antifungal drugs along with the paucity of antifungal drugs warrants novel drugs to treat invasive fungal infections. In this study, we investigated the antifungal activity of a novel series of diazahexa/hepta cyclic cage-like compounds. Results indicate that compounds with unsubstituted and o-methyl substitution on aryl rings exhibit potent broad-spectrum antifungal activity against various fungal strains. In addition, these compounds showed significant inhibitory activity against Candida hyphae and biofilm formation. Collectively, results from this study indicate that these compounds are promising candidates to develop as novel antifungal drugs to treat drug-resistant fungal infections.