Candida haemulonii complex has emerged as notorious yeasts causing invasive infections with high rates of treatment failures. Since there is a particular interest in the development of non-mammalian host models to study microbial virulence, with the aim to evade the ethical impact of animal tests, herein we compared the virulence of C. haemulonii, C. duobushaemulonii and C. haemulonii var. vulnera with non-albicans Candida species (C. tropicalis, C. krusei and C. lusitaniae) on Galleria mellonella and the efficacy of antifungal drugs. All these fungi induced a dose-dependent effect on larvae killing, a decrease in hemocyte density and fungi were phagocytozed by hemocytes in equal proportions. Fungal inoculation caused early larvae melanization after some minutes of injection, followed by an augmented pigmentation after 24 h. Differences among species virulence can be explained, in part, by differences in growth rate and production of hydrolytic enzymes. First-line antifungals were tested with equivalent therapeutic doses and MIC profile in vitro was correlated with in vivo antifungal efficacy. Additionally, fungal burden increased in infected larvae along time and only caspofungin reduced the number of CFUs of C. haemulonii species complex. So, G. mellonella offers a simple and feasible model to study C. haemulonii complex virulence and drug efficacy.