Infection with antibiotic-resistant bacteria is becoming a significant public health risk. In this study, we synthesized a series of imidazolium salt (IMS)-containing polymers and hydrogels and tested their antimicrobial properties against both gram-positive (Staphylococcus aureus and MRSA) and gramnegative (Escherichia coli and PA01) bacteria. IMSs were either grafted as side chains or functionalized in the main chain of linear polymers, which demonstrated antimicrobial properties with minimum inhibitory concentrations as low as 2 lg/mL. Similarly, the optimized IMS-containing hydrogel effectively killed MRSA with a 96.1% killing efficiency and inhibited the growth of PA01. These hydrogels also demonstrated high performance in terms of mechanical property (compressive strength >2 MPa) and were noncytotoxic toward human dermal fibroblasts.