A sustainable method has been employed for the production of a biomedical material in an economical way. Among biomedical polymers, two mostly used polymers are silicones (PDMS) and polyurethanes (PU). PDMS can outperform other polymers due to its biocompatibility and flexibility, but its high cost became a major roadblock for many applications. PU can be produced from a variety of sustainable resources in a cost effective manner. In this work, vegetable oil-based PU is blended with PDMS to produce a biomedical material which can contribute to the economy and environment. In this method, siliconized epoxy-terminated polyurethanes (EPDMS) were prepared from castor oil, 4,4' methylene-bis-(cyclohexyl isocyanate), glycidol, and hydroxy-terminated poly-(dimethyl siloxane) (HTPDMS). The properties of the resulting products were compared with virgin PU with a NCO/OH ratio of 1.2:1 and epoxy-terminated PU (EPU) with a polyol/diisocyanate/glycidol ratio of 1:3:3. The structural elucidation of PU, EPU, and EPDMS were carried out by FTIR and (HNMR)-H-1 spectroscopic techniques. The effect of incorporation of siloxane and glycidol on the thermal properties of PU was analyzed by thermogravimetric analysis and differential scanning calorimetry analysis. The improved hydrophobicity of the EPDMS was observed from water contact angle measurements. The surface morphology was examined using atomic force microscopy analysis. In vitro cytotoxicity analysis revealed the cytocompatibility of the EPDMS which makes them suitable for biomedical applications.