Thermal plastic polyurethanes (TPUs), serving as biomaterials, have become increasingly prevalent over time in many fields including artificial blood vessels, pericardial patches and other tissue engineering scaffolds by virtue of well adjustable performance. However, synthetic polyurethanes are, to some extent, inadequate for their cytocompatibility and biological activity owing to high hydrophobicity and lack of active groups. In this study, an amino-terminated bis(L-arginine) alkylene diester extender (L-Arg-8) was synthesized and Arg-based biodegradable poly(ester urea) urethanes (PEUUs) with different content of arginine groups were designed, synthesized and characterized in regard to the amelioration of the biodegradability, hydrophilicity and cytocompatibility of thermoplastic polyurethanes (TPUs) with PCL as soft segments. Biodegradability, hydrophilicity and positive surface charges increased after Arginine was introduced. As cytocompatibility was improved, PEUU materials A8-1.2 and A8-1.6 were proved to be suitable for human dental pulp stem cells (hDPSCs) to adhere, grow and proliferate on in vitro. These materials would unlock great potential for the use in tissue engineering and regeneration. Additionally, halloysite nanotubes (HNTs) were composited to PEUUs for further exploration to the applications in bone tissue. The addition of halloysite nanotubes further stimulated the osteogenic differentiation of human dental pulp stem cells in vitro. At the same time, a rat cranial defect model was built to assess effects of repair in vivo. Osteointegration and repair were promoted by patch-implanted groups. A8-1.2 6% HNTs showed the best repair. All the results indicated that Arg-based poly(ester urea) urethanes and the composites were conductive to bone repair.