Sericin (SS), a silk-derived protein, possesses numerous advantages such as biocompatibility and non-toxicity, making it a promising material for hydrogel fabrication in biomedical and pharmaceutical fields. Progesterone (PRO), a natural hormone essential for regulating key physiological functions such as preparing the female body for conception and pregnancy, faces challenges due to its low water solubility. Therefore, effective formulations are required to enhance its solubility and bioavailability. In this study, a hydrogel was synthesized through a simple blending method at room temperature using SS and polyethylene glycol (PEG), a widely used synthetic polymer in biomedical fields. The primary objective of this formulation was to achieve controlled release of PRO, thereby improving its therapeutic efficacy and patient compliance. Various characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA), were employed to evaluate the hydrogel's structural, morphological, and thermal properties. The swelling behaviour and drug release kinetics of the hydrogel were analysed, confirming its suitability for controlled delivery of PRO. Molecular docking studies shows possible binding sites of PRO with SS and PEG. Furthermore, toxicity studies demonstrated the hydrogel's significant non-toxic behaviour. Most importantly, the synthesized hydrogel offers potential applications in the biomedical field due to its simple fabrication process, biocompatibility, and effective controlled release of hydrophobic drug PRO, making it a promising candidate for controlled drug delivery systems.