Developing coating materials with low cytotoxicity and high antimicrobial activity has been recognized as an effective way to prevent medical device-associated infections. In this study, a maleic anhydride terpolymer (PPTM) is synthesized and covalently attached to silicone rubber (SR) surface. The formed coating can be further cross-linked (SPM) through the self-condensation of pendent siloxane groups of terpolymer. No crack or delamination of SPM was observed after 500 cycles of bending and 7 day immersion in deionized water. The sliding friction force of a catheter was reduced by 50% after coating with SPM. The SPM coating without adding any extra antibacterial reagents can kill 99.99% of Staphylococcus aureus and Escherichia coli and also significantly reduce bacterial coverage, while the coating displayed no antimicrobial activity when maleic anhydride groups of SPM were aminated or hydrolyzed. The results of the repeated disinfection tests showed that the SR coated with SPM could maintain 87.3% bactericidal activity within 5 cycles. Furthermore, the SPM coating only imparted slight toxic effect (>85% viability) on L929 cells after 36 h of coculture, which is superior to the coating of aminated SPM conjugated with the antimicrobial peptide E6. The terpolymer containing maleic anhydride units have great potential as a flexible and durable coating against implant infections.