Fibrosis is characterized by excessive deposition of extracellular matrix (ECM), which disrupts normal tissue structure and function. Fibronectin, a major ECM glycoprotein, plays an important role in this process by promoting fibroblast activation and differentiation into myofibroblasts. Fibronectin-binding peptides have shown potential as anti-fibrotic agents by interfering with ECM assembly, but their therapeutic application is often limited by rapid renal clearance and short systemic circulation. To address these limitations, we developed a long-acting peptide-polymer conjugate based on an a fibronectin-binding peptide. A site-specifically engineered peptide was conjugated to a polymer and purified using chromatography methods. In vitro binding assays confirmed that the engineered peptide retained its binding affinity for fibronectin following polymer conjugation. Furthermore, functional studies demonstrated that the conjugates preserved anti-fibrotic activity in cell-based matrix assembly assays. Ongoing in vivo studies are evaluating the pharmacokinetics and therapeutic potential of these peptide–polymer conjugates as ECM-targeted therapies for fibrotic diseases.