Background: Testing microbial virulence in mammals is a prerequisite before applying therapeutic agents to humans. However, conducting experiments in mammalian models is expensive and requires ethical considerations. Therefore, insects have been widely used as an alternative model to study human microbial virulence. Aim: This work aimed to evaluate the use of Galleria mellonella larvae as a model for testing the virulence factors of the human pathogenic fungi, Candida albicans, and Aspergillus fumigatus. Fungal-induced influences on mortality and various immunological and histological parameters were also evaluated and compared. Materials and methods: Virulence was assessed by including hemocyte density, melanin formation, phenoloxidase (PO) activity, and cytotoxic effects were evaluated as indicators of fungal virulence. Results: Our findings, collected from survival tests and time post-infection, revealed interspecific differences, more pronounced with C. albicans than with A. fumigatus, and an increasing burden of infected larvae over time. The differences may be partially elucidated by disparities in growth rate and the production of hydrolytic enzymes of the tested fungi. Challenged larvae with either fungal species exhibited a notable reduction in circulating hemocytes and hemolymph protein content, a significant increase in melanin formation, phagocytosis, and PO activity, along with pronounced cytotoxic effects in the cuticle and midgut. Conclusion: We can conclude that G. mellonella larvae constitute a simpler and more suitable model for studying the virulence of many fungal species.