Transdermal drug delivery systems (TDDS) are used as an alternative route to deliver drugs into the blood system for therapy. The matrix materials that have been widely used in TDDS are hydrogels. The dextran hydrogels were prepared by the solution casting using trisodium trimetaphosphate (STMP) as the crosslinking agent, and diclofenac sodium salt (Dcf) as the anionic model drug. Poly(2-ethylaniline) (PEAn) was successfully synthesized and embedded into the dextran hydrogel as the drug encapsulation host. The in-vitro release of Dcf from the hydrogels was investigated using a modified Franz-Diffusion cell in a phosphate-buffered saline (PBS) solution at the pH of 7.4 and at 37 °C for a period of 24 h, under the effects of crosslinking ratios, dextran molecular weights, electric potentials, and the conductive polymer PEAn. The release mechanism of Dcf from the dextran hydrogels and the composite without electrical potential was the diffusion controlled mechanism or the Fickian diffusion. Under applied electrical potentials, the release mechanism was a combination between the Fickian diffusion and the matrix swelling. The Dcf diffusion coefficients from the dextran hydrogels without electrical potential increased with decreasing crosslinking ratio and molecular weight. Under electrical potentials, the corresponding diffusion coefficients were much higher due mainly to the electro-repulsive force between the negatively charged electrode and the negatively charged dextran and the induced dextran expansion. For the Dcf-loaded PEAn/dextran composite, the diffusion coefficient was enhanced by two orders of magnitude when the electric potential was applied, specifically illustrating the unique features of PEAn as an efficient drug encapsulation host without electric field, and as a drug release enhancer under electric field through the reduction reaction.