The aim of this work is to obtain optically and biologically active poly(urethane-imide)s (PUIs) using N,N'-(pyromellitoyl)-bis-l-tyrosine dimethyl ester (5) as a chiral and biologically active diphenolic monomer. Step-growth polymerization of diol 5 with various aliphatic and aromatic diisocyanates was carried out by gradual heating technique. The resulting PUIs were characterized with FT-IR, and two of them by H-1-NMR spectroscopy and elemental analysis. Thermogravimetric analysis and differential scanning calorimetry were used to determine the thermal properties of the two representative PUIs. The morphology of polymer was studied by X-ray diffraction analysis. Furthermore, in vitro toxicity and biodegradability behaviors of the obtained PUIs were studied in culture media and soil burial degradation which reveals that the synthesized polymers are biologically active and biodegradable in natural environment.