We designed a library of 24 cyclic peptides containing arginine (R) and tryptophan (W) residues in a sequential manner [R<sub><i>n</i></sub>W<sub><i>n</i></sub>] (<i>n</i> = 2-7) to study the impact of the hydrophilic/hydrophobic ratio, charge, and ring size on the antibacterial activity against Gram-positive and Gram-negative strains. Among peptides, <b>5a</b> and <b>6a</b> demonstrated the highest antimicrobial activity. In combination with 11 commercially available antibiotics, <b>5a</b> and <b>6a</b> showed remarkable synergism against a large panel of resistant pathogens. Hemolysis (HC<sub>50</sub> = 340 μg/mL) and cell viability against mammalian cells demonstrated the selective lethal action of <b>5a</b> against bacteria over mammalian cells. Calcein dye leakage and scanning electron microscopy studies revealed the membranolytic effect of <b>5a</b>. Moreover, the stability in human plasma (<i>t</i><sub>1/2</sub> = 3 h) and the negligible ability of pathogens to develop resistance further reflect the potential of <b>5a</b> for further development as a peptide-based antibiotic.