The antifungal and antimicrobial activities of three pentacycloundecane (PCU) tetra-amine derivatives are reported herein. The in vitro activity of these PCU derivatives against yeasts (Candida albicans and non-albicans species) and filamentous fungi was evaluated using the Clinical and Laboratory Standards Institute (CLSI) M27-A2 and M38-A2 guidelines and the 2H-tetrazolium salt, (MTS) colorimetric method. The minimum inhibitory concentration against most of the tested clinical fungal strains for GKM8 and GKM9 derivatives ranges from 15.6 to 62.5 μg/mL while GKM11 ranged from 3.9 to 7.8 μg/mL. The GKM11 derivative was also active against fluconazole-resistant strains of fungi. The GKM11 derivative also exhibited promising activity against filamentous fungi in that it was 2.5 times more active than amphotericin B against Sporothrix schenckii. Antibacterial activity was determined using the broth microdilution method (BMM) and the iodonitrotetrazolium chloride (INT) colorimetric method. The GKM11 derivative was mainly active against Gram-positive bacteria with MIC ranging from 3.9 to 7.8 μg/mL. Activity against Gram-negative bacteria tested was limited to Escherichia coli and Elizabethkingia meningoseptica (MIC of 31 μg/mL).