Microbial colonisation of synthetic materials is a great concern in many fields, e.g., in implant surgery and medical devices; therefore biocompatible hydrophilic organic materials with inherent antimicrobial properties are of current research interest. In this work, we describe the preparation of antibacterial and biocompatible polymeric film based on N-vinyl-2-pyrrolidone (VP) and 2-hydroxyethyl acrylate (HEA), using ethyleneglycol dimethacrylate (EGDMA), and synthetic acrylic monomer containing sulfadiazine chemically anchored. The synthesised polyvinylpyrrolidone (PVP)-based films were characterized by different techniques (1H and 13C NMR, ATR-FTIR, SEM, and TGA). In this study, the biophysical responses of bacteria and L929 cells towards the prepared materials as model device surfaces were evaluated. The membrane that contains the anchored sulfadiazine moiety showed excellent antibacterial activity against Escherichia coli as well as good biocompatibility. Based on the experimental results, this material is a good candidate for medical applications as a biomaterial.