Bioadhesives are crucial in minimally invasive procedures but often lack biocompatibility, mechanical strength, and antimicrobial properties. Polyurethane-based adhesives, particularly UV-curable types, offer tunable properties and rapid curing. This study developed a polyurethane-acrylate adhesive system incorporating sericin and gentamicin to enhance biocompatibility and antibacterial effects for surgical and wound care applications. Sericin, a silk-derived protein, improved cell adhesion without compromising structural integrity, while 2.5 % gentamicin provided sustained antibacterial activity against E. coli, P. aeruginosa, and S. aureus. The synthesis involved modifying IPDI with β-cyclodextrin, sericin, and PEG (200, 400, 600) to optimize flexibility and stability. Comprehensive characterization was conducted, including FTIR, TGA, DSC, NMR, SEM, AFM, adhesion strength, biodegradability, gentamicin release, antibacterial efficacy, and biocompatibility with L-929 fibroblast cells. Adhesion strengths were 4141.3–4474.7 kPa (PEG200), 2306–3158 kPa (PEG400), and 1690–2061 kPa (PEG600), with PEG400 providing the best balance, making IPDI-SER-P400-20-AC the optimal candidate. The adhesive exhibited 87 % cell viability (ISO 10993-5), 30 % biodegradation in four weeks, and 60 % gentamicin release within 24 h, ensuring rapid antibacterial action. This sericinand gentamicin-enhanced bioadhesive offers a promising multifunctional platform for biomedical applications, with potential for further optimization in controlled drug release and long-term in vivo evaluations.