Three different types of solid dispersions based on polyvinyl polymers and related copolymers (Kollidon® VA64, Soluplus® and Kollicoat IR®) comprising polydatin-rich Polygoni cuspidati extract were prepared by hot melt extrusion. The systems were characterized using X-ray powder diffraction, infrared spectroscopy as well as by polydatin release and in vitro permeability. Mucoadhesive tablets were prepared from the extrudates based on Kollidon® VA64 and Soluplus® to obtain a suitable pharmaceutical form, where (hydroxypropyl)methyl cellulose was added as a mucoadhesive agent. The tablets were evaluated in terms of the kinetics of polydatin release as well as their mucoadhesive properties. The best tabletability properties, polydatin release profile and adequate mucoadhesive properties were obtained by the formulation containing the Kollidon® VA64-based extrudate, which makes it an excellent prototype for enhancing the release of poorly water-soluble compounds.