Biological systems possess unique non-equilibrium functions, maintaining tight manipulation of their surroundings through inter-communication of multiple components and self-regulatory capability organized over different length scales. However, most artificial materials are incapable of communicating and self-regulating behavior due to their limited number of component and direct responsive modes. Herein, a new integrated self-regulation system is developed utilizing stimuli-responsive polyelectrolyte capsules as building blocks. The combination of stimuli-responsive capsules and enzyme immobilized microgels is designed to mimic life systems and its programmable interactive communications and self-regulation behavior is demonstrated through communication-feedback mechanism. Polyelectrolyte capsules can sense changes of their surrounding, then start the internal communication by releasing energy-rich cargo mimicking the behavior of the cells. The microgel particles subsequently complete closed-loop communication through providing negative feedback on capsules by enzymatic reaction and actuating pH-regulation of the whole system. Different communication modes and pH-regulation behaviors could be achieved by adjusting spatial and kinetic conditions. Proposed intelligent system is highly customizable due to the wide selection of encapsulated cargos, stimuli-responsive blocks and reaction networks, and would have broad influences in areas ranging from medical implants that assist in stabilizing body functions to microreactor system that regulate catalytic reactions.