Two unique ionic covalent organic networks (iCONs) incorporated with guanidinium motifs were obtained and characterized by various techniques. Upon 8 h of treatment with iCON-HCCP (250 μg/mL), >97% killing of Staphylococcus aureus, Candida albicans, and Candida glabrata strains was observed. Antimicrobial efficacies against bacteria and fungi were also evident from FE-SEM studies. High antifungal efficacies also correlated well with >60% reduction of ergosterol content, high lipid peroxidation, and membrane damage leading to necrosis.