In this study, biocompatible and biodegradable polyurethanes (PUs) were prepared by using different amino acids as chain extenders. Their structure and morphology were determined by fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis whereas their mechanical properties were evaluated by universal testing machine. These PUs were not only screened for their in vitro and in vivo cytotoxicity but also evaluated for their water uptake, swelling behavior, hydrolytic degradation and employed as pH-responsive drug delivery carriers. An anti-cancer drug imatinib was loaded to these PUs with 94% of loading efficiency and its release behavior was studied at different pH values. All the PUs showed a persistent local release for > 300 h. The results exhibited that drug released at physiological pH (7.4) is far lesser as compared to the acidic and basic pH of the release media. At acidic pH, 82% of the drug has been released as compared to the 41% at physiological pH. The results clearly demonstrate that these PUs are safe and can be used as intelligent drug release matrices for targeted drug delivery.