Compositions and methods of making and using thereof are provided with a specific antimicrobial activity and efficacy toward Gram-positive and Gram-negative bacteria and low levels of toxicity toward mammalian cells. The compositions include water-soluble molecules characterized by a hydrophobic interior fragment and side groups containing cationic groups. A class of these molecules is provided with variations in the length of the internal conjugated segment and in other molecular features, which impact the efficacy and toxicity. The substituents on the cationic functional group, the structural variations on the solubilizing group, and the length of the conjugated segment are important features affecting the antimicrobial property and the non-toxicity to mammalian cells of the composition.