AbstractAntibiotic resistance has become a critical issue, alarming the healthcare and agriculture sectors worldwide. Thanks to rapid advancements in polymer science, antimicrobial polymers (AMPs) have been developed as a mimic version of host‐defense peptides (a part of natural immune systems of multicellular organisms) to mitigate antibiotic resistance. By exploiting advanced polymerization techniques, polymer structures are easily manipulated in a well‐defined controlled manner, enabling precise and accurate evaluation of the structure–activity relationship. Recent years have witnessed the blossoming of antimicrobial polymer development. This review provides comprehensive insight into antimicrobial polymers from concept to structure design, to biofunction control. Along with the optimization of intrinsic factors, including compositional and topological features, external factors like induced conformation upon exposure to specific targeting pathogens should be considered in AMP design and optimization. Furthermore, the new design approaches of smart response platforms (or bacterial‐induced triggering systems) and targeting specific administration dosage forms for specific pathogens are also discussed as prospective strategies to address the remaining challenge of toxicity while maintaining or even enhancing antimicrobial potency.