A bioassay-guided fractionation of the extract of the fungus Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai, led to the isolation of antibacterial compounds viriditoxin and its monomeric subunit semi-viriditoxin. Viriditoxin showed significant antibacterial activity against several marine fish and human pathogens including MDR strains. Significant potencies against resistant pathogens such as VRE Enterococcus faecium, VRE Enterococcus faecalis, and MRSA were highly interesting. Viriditoxin also showed notable antibacterial activity against the fish pathogen Streptococcus iniae. Its potency was over 100-fold higher than oxytetracycline which is employed as a general antibiotic for aquaculture.