This study describes a facile and high yielding route to two series of polymethacrylates inspired by the naturally occurring, tryptophan-rich cationic antimicrobial polymers. Appropriate optimization of indole content within each gave rise to polymers with high potency against Staphylococcus epidermidis (e.g., PGI-3 minimum inhibitory concentration (MIC) = 12 ?g/mL) and the methicillin-resistant strain of Staphylococcus aureus (e.g., PGI-3 MIC = 47 ?g/mL) with minimal toxicity toward human red blood cells. Future work will be directed toward understanding the cooperative roles that the cationic and indole pendant groups have for the mechanism of these polymers.