Cryptococcosis is a devastating fungal disease associated with high morbidity and mortality even when treated with antifungal drugs. Bionized nanoferrite (BNF) nanoparticles are powerful immunomodulators, but their efficacy for infectious diseases has not been investigated. Administration of BNF nanoparticles to mice with experimental cryptococcal pneumonia altered the outcome of infection in a dose response manner as measured by CFU and survival. The protective effects were higher at lower doses, with reductions in IL-2, IL-4, and TNF-α, consistent with immune modulation whereby reductions in inflammation translate into reduced host damage, clearance of infection, and longer survival.