Indolicidin, a 13-residue cationic AMP derived from bovine neutrophils, targets DNA and exhibits broad-spectrum antimicrobial activity . Rich in tryptophan and proline residues, it adopts a random coil structure both in solution and when bound to micelles (PDB IDs: 1g8c, 1g89) [149]. Indolicidin's amphipathicity, net positive charge, and C-terminal amidation contribute to its DNA-binding ability , which interferes with bacterial DNA biosynthesis through hydrogen bonding, salt bridges, and aromatic stacking interactions (Figure ). While Indolicidin interacts with multiple intracellular targets , its non-specific binding confers a "dirty drug" profile, impacting various DNA biosynthesis enzymes. Indolicidin serves as a valuable case study in understanding how targeted modifications can selectively direct its activity against either Gram-positive or Gram-negative bacteria by fine-tuning its multiple mechanisms of action.