Hot-melt extrusion has been used as the convenient processing to produce drug release carriers, by virtue of a series of advantages, including solvent free, continuous processing and great efficiency. Polymers with different water solubility are combined to achieve different release behaviors, resulting from the dispersion of water-soluble polymer in the blends. However, the morphology of water-soluble dispersion phase is limited by using the conventional extrusion processing, thus it is difficult to adjust the drug release behavior of polymer blends. Herein a unique processing named multistage stretching extrusion was employed to vary the dispersion of water-soluble polymer in the matrix, with an assembly of laminating-multiplying elements (LMEs, which divide and recombine polymer melts). Thus, controllable and flexible drug release behavior was achieved, due to the various drug diffusion channels obtained through the dispersion of water-soluble phase. Poly(ƒÕ-caprolactone) (PCL) and polyethylene oxide (PEO) were used to manufacture polymer blend, and ibuprofen was used as the model drug. In order to obtain different dispersion morphology and drug release behavior, various experimental parameters were investigated, including the number of LME, polymer melting viscosity of PCL and PEO, the drawing rate of the melt, and the drug loading of the matrix. Various drug release behaviors were achieved, without compromising the physical integrity of the polymer blends, and the release mechanisms were discussed. The multistage stretching extrusion thus provided to be a unique solution for the controlled delivery of various therapeutic agents.