In recent years, there has been increased interest in biodegradable polyurethanes for use in regenerative medicine because of their versatility and biocompatibility. Nevertheless, these polymers are usually produced using organic solvents that can lead to the release of toxic components. In this work, polyurethane/montmorillonite nanocomposites were designed to work as guided tissue regeneration membranes to treat periodontal diseases. Polyurethanes were synthesized in an aqueous environment. The composition, morphology, and mechanical properties of the biomaterials were evaluated. The cellular viability, proliferation, and morphology changes of rat culture cementoblasts were also investigated using a montmorillonite assay. Small-angle X-ray scattering, X-ray diffraction, and infrared spectroscopy results showed that the degree of clay delamination within the polymer was able to tailor the phase morphology of the polymer, the chemical aspects of the surface, the mechanical properties, and the kinetics of hydrolysis of the materials. The produced scaffolds provided a good environment for the adhesion and proliferation of cementoblasts and thus can be considered suitable biomaterials for participating in procedures associated with periodontal regeneration.