Advances in technology allow for the construction of synthetic antibiotics, which includes the development of de novo antimicrobial peptides (AMPs). The contents of AMPs including amino acids, chain length, hydrophobicity, ring structure/rigidity, terminus and charge when modified can alter the antimicrobial properties. A special family of peptides called histatins is naturally excreted by oral glands as an immune response, and previous research shows their potential for treating thrush. Histatin 8 is known to have antimicrobial activity against yeast strains and the goal of this study was to synthesize histatin 8 and two novel derivatives (delt 1 and delt 4) that fall at extremes of each other with regard to charge and hydrophobicity in order to investigate the properties that could optimize antimicrobial properties. The derivatives were characterized using various chemical and biological assays to investigate the effects of charge and hydrophobicity on bioactivity. Compared to histatin 8, delt 4’s minimum inhibitory concentration (MIC) was decreased more than tenfold against Candida tropicalis indicating increased antimicrobial activity. Re-inoculation confirmed fungicidal properties.