This work describes the enzymatic degradation of combined hollow capsules via layer‐by‐layer (LbL) self‐assembly technique. They previously showed the build‐up and characterization of capsules composed of synthetic [Poly(sodium 4‐styrene‐sulfonate)/Poly(allylamine hydrochloride)] and biodegradable (Heparin/Chitosan) polyelectrolytes. Biocatalytic response of assembled multilayer capsules provides a more functional and oriented approach in controlled release of encapsulated molecules: in this case multilayer capsule was disassembled by heparinase. Morphological change of individual capsule was assessed with Atomic Force Microscopy and Confocal Laser Scanning Microscopy. The sustained release of encapsulated FITC‐Dextran model was realized under enzymatic degradation of the capsule shells by heparinase. The release profile of FITC‐Dextran indicated the successful control in a concentration‐dependent manner, which shows the applicability as smart drug delivery system