Poly(ε-caprolactone) (PCL) and polyethylene oxide (PEO) have been widely used in drug release and tissue engineering due to their excellent biocompatibility, nontoxicity and low melting point. The combinations of the two polymers are realized to adjust the release behavior of loaded drugs. However, the composites usually exhibited a burst release within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Herein we considered a unique alternating multilayered structure to adjust the drug release behavior. Due to their flexible structure with hundreds or thousands of alternating layers, various drug release systems are easily realized. Furthermore, it is demonstrated that the dispersion of loaded drugs and the degradation of the matrix are significantly varied by virtue of the variation of polymer crystallization. Thus, it is very profound to investigate the crystallization behavior of PCL/PEO multilayered composites, as well as their effect on the dissolution and the drug release of the matrix. DSC, hot stage POM, micro-FTIR and 2D-WAXD are employed to determine the crystallization behavior of the composites, the weight loss and in-vitro test are used to research the dissolution behavior and drug release property of the composites. It is speculated that the crystallization behavior of PEO can be easily affected by growing space and the interface of the layers, resulting from the large spherulite size of PEO (about 160 μm). On the other side, because PCL has a much smaller spherulite size of about 8 μm, the effect of multilayered structure on the PCL crystallinity is negligible. This unique alternating multilayered structure can easily affect the dissolution behavior of PCL/PEO multilayered composites, and it is demonstrated to be a potential candidate to achieve different release requirements.