Hydrogels have emerged as a potential tool for enhancing bioavailability and regulating the controlled release of therapeutic agents. Owing to its excellent biocompatibility, silk sericin-based hydrogels have garnered interest in biomedical applications. This study focuses on synthesizing a soft hydrogel by blending silk sericin (SS) and polycaprolactone (PCL) at room temperature. The physicochemical characteristics of the hydrogels have been estimated by different analytical techniques such as UV− visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The rheological studies demonstrate the non-Newtonian behavior of the hydrogels. Further, the porosity analysis indicates a commendable absorption capacity of the hydrogels. The swelling degree of the hydrogels has been checked in both distilled water and buffer solutions of different pHs (2−10). Moreover, the drug release profile of the hydrogels, using diclofenac sodium (DS) as a model drug, has revealed a substantial release of approximately 67% within the first 130 min with a drug encapsulation efficiency of 60.32%. Moreover, both the empty and the drug-loaded hydrogels have shown antibacterial properties against Gram-positive and Gram-negative bacteria, with the drug-loaded hydrogels displaying enhanced effectiveness. Additionally, the prepared hydrogels are biodegradable, demonstrating their future prospects in biomedical applications.