AbstractBacterial colonization and biofilm formation on the surface of materials can lead to serious bacterial infections and are highly detrimental to our health. Here, we prepared a water‐insoluble HPL‐DOSS complex by compounding hyperbranched polylysine (HPL) with docusate sodium salt (DOSS) and coated HPL‐DOSS onto the surfaces of the commercial polypropylene (PP) and thermoplastic polyurethane (TPU) plastics to afford antibacterial PP‐HD and TPU‐HD plastics. PP‐HD and TPU‐HD showed excellent antibacterial activities against both Escherichia coli and MRSA. In addition, the bacterial residues on the PP‐HD and TPU‐HD surfaces were significantly reduced compared with the pristine PP and TPU surfaces, indicating that the HPL‐DOSS surface coating had good anti‐adhesive property against bacteria and helped to reduce the formation of biofilms. Meanwhile, both PP‐HD and TPU‐HD exhibited excellent biocompatibility, indicating that the HPL‐DOSS complex could be used as a safe antimicrobial coating material to reduce bacterial infections on plastic surfaces.