Sepsis, a life-threatening disruption, remains a significant global healthcare challenge that urgently needs novel strategies to improve management. This study aimed to develop multifunctional vancomycin-loaded polymersomes (VCM-HA-SIL-Ps) using a novel hyaluronic acid-silybin (HA-SIL) conjugate to target the TLR inflammatory pathway and enhance VCM's efficacy against bacterial sepsis. HA-SIL was synthesized and characterized by FT-IR, UV-Vis spectroscopy, and