The multilayered drug controlled release materials consisting of alternating pure polymer (PCL) layers, acted as barrier layers and PCL/Polyethylene oxide (PEO)/Metoprolol tartrate (MPT) blend layers as drug-loaded layers were fabricated through layer-multiplying co-extrusion. As a type of well-defined and flexible co-continuous morphology, the multilayer structure had controllable number of layers and layer space. Permeability of phosphate buffer could be modified by varying the thickness of drug-loaded layers, which were restricted by adjacent barrier layers and the content of hydrophilic component in drug-loaded layers. Therefore, the interrelation between the morphological evolution and the drug release behavior of the alternating multilayered materials was investigated. Experimental results indicated that due to the restriction of barrier layers, the dissolution rate of PEO declined with the increase of layer number, resulting in the release rate of MPT decreased. In addition, the decrease of hydrophilic component content in drug-loaded layers led to the decline of release rate of MPT. More importantly, this unique alternating multilayered structure also showed outstanding mechanical properties and degradation stability performances, and it is demonstrated to be a potential candidate to achieve different release requirements.