Infections have accounted for the majority of failures in implants over the past decades. Host defense peptide mimicking polymers have been considered as one of the promising antimicrobial candidates for their cost-effective synthesis, broad-spectrum antimicrobial activity, low propensity to induce drug resistance, and remarkable biocompatibility. In this review, covalent-grafting strategies are mainly discussed to tether host defense peptide mimicking polymers on surfaces, aiming to obtain potent antimicrobial activity. In addition to the antimicrobial function, we review the antimicrobial mechanism of these polymer-modified antimicrobial surfaces in precedent literatures. We also review the subcutaneous implant infection models that are critical assessments for potential biomedical applications. In the end, we provide our perspective on the future development of this field, especially for biomedical applications.