The continuing rise in antibiotic and multi-drug resistant bacterial infections is a major global medical health issue, which is not being met by traditional antibiotic research. Here, we show that a new class of antimicrobial agents, termed ‘Structurally Nanoengineered Antimicrobial Polypeptide Particles’ (SNAPPs), synthesized using ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) to produce star-shaped polypeptide nanoparticles exhibit potent antibacterial activity. By altering the star-polymer arm length and number of radial arms per polymer using different monomer concentrations and dendrimer initiators we show that the SNAPPs target different bacteria. Further by end-capping the polymer arms with fatty acids we were able to investigate the effect of adding different alkyl chains (C4-C18) to antimicrobial activity and their cytotoxicity. In addition, the amino acid composition of the star polymers arm has a significant impact on antimicrobial activity. We synthesised SNAPPs containing all L-amino acids, a combination of D-, L- amino acids and all D-amino acids, each SNAPP contained a cationic residue polymerized with a hydrophobic or polar/neutral amino acid. Surprisingly the cationic/polar amino acid combination and a D-, L- combination proved to be the most efficacious against a range of drug sensitive and multidrug resistant bacterial strains. Further, we demonstrate that the different chemical modifications have a targeting and altered mode of action from our initial parent SNAPP. Overall, our study demonstrates the potential of SNAPPs as direct antimicrobial agents and the versatility of the peptide polymer chemistry to produce highly novel therapeutics to treat bacterial infections.