Bacteria continuously develop resistance to conventionally-prescribed antibiotics; thus, the need for new antibacterial agents is pressing. Natural products from Hawaiian marine plants were tested for activity against Mycobacterium tuberculosis, Methicillin-resistant Staphylococcus aureus, and Bacillus anthracis in a novel approach to target the trans-translation pathway. The performed screens identified natural products able to inhibit growth and kill pathogenic bacterial cells, introducing a prospective source of new drugs to combat the threat of growing resistance to antibiotics.