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Pseudomonas aeruginosa significantly induces health-associated infections in a variety of species other than humans. Over the years, the opportunistic pathogen has developed resistance against commonly used antibiotics. Since most P. aeruginosa strains are multi-drug resistant, regular antibiotic treatment of its infections is becoming a dire concern, shifting the global focus towards the development of alternate antimicrobial approaches. Pyocins are one of the most diverse antimicrobial peptide combinations produced by bacteria. They have potent antimicrobial properties, mainly against bacteria from the same phylogenetic group. P. aeruginosa, whether from clinical or environmental origins, produce several different pyocins that show inhibitory activity against other multi-drug-resistant strains of P. aeruginosa. They are, therefore, good candidates for alternate therapeutic antimicrobials because they have a unique mode of action that kills antibiotic-resistant bacteria by attacking their biofilms. Here, we review pseudomonas-derived antimicrobial pyocins with great therapeutic potential against multi-drug-resistant P. aeruginosa., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)