Herein, we use in situ vapor phase polymerization (VPP) of pyrrole (Py) on an oxidant-impregnated thermoplastic polyurethane (TPU) matrix comprising a three dimensional eco-friendly sugar particle assembly to produce a soft, flexible, and conductive polypyrrole (PPy)-TPU hybrid scaffold. The selective removal of sugar assembly yielded a highly porous skeletal structure, with the effective penetration, diffusion, and polymerization of Py resulting in uniform PPy formation both on the surface and the inner side of the TPU matrix. The mechanical and electrical properties of the obtained scaffold were investigated by bending and stress?strain and electrical measurements. The electrical resistance of the scaffold prepared by 12 h polymerization, equaled 1 MΩ and did not significantly change after 100 fold bending. In vitro biocompatibility was investigated by MC3T3-E1 cell culturing with cell viability evaluated using the WST assay. Thus, the soft and flexible PPy-TPU hybrid scaffold produced by VPP might be practically useful, implying that this preliminary investigation needs to be extended to study the behavior of muscle and nerve cells under electrical stimulation.