Emergence of resistance against existing antifungal drugs created a need to find out new structural classes of antifungal agents. Defensins are significant vertebrate antifungal peptides which target the capsule of Cryptococcus neoformans. The cryptococcal capsule is an important virulence factor and its main component is the polysaccharide glucuronoxylomannan (GXM). In this study, we design a new structural class of antifungal peptidomimetics of human neutrophil peptides (defensins). Bioinformatics tools were used to predict level of sequence similarity amongst them. Peptidomimetics of human neutrophil peptides (HNPs) were designed which showed better binding with GXM of Cryptococcus than natural human neutrophil peptides (HNPs) and could be used as potential drug candidates against cryptococcal infections.