New series of N-(2,3,3-triiodoallyl) and N-(3-iodopropargyl) azole derivatives (100 compounds) involving pyrrole, pyrazole, imidazole, triazole, and tetrazole nuclei were synthesized successively with the aid of quantitative structure-activity relationship (QSAR) analysis to obtain potent antifungal agents. Starting from the derivatives of nitropyrrole-containing antibiotics, the QSAR analysis of the pyrrole derivatives against Candida albicans and Trichophyton mentagrophytes strains indicated the positive contribution of the nitro group and negative effect of the size of molecule. Further application of the QSAR analysis on the multi-azole derivatives revealed the importance of hydrophobicity and electronegativity as well as steric effect to the activities and led to the synthesis of one of the most potent iodo compounds, 2-(2,3,3-triiodoallyl)tetrazole (67, ME1401).