A new enzymatic chemo-mechanical actuator that can convert the chemical energy of glucose into mechanical energy for an autonomous drug release system without electrical power was developed and demonstrated. The glucose- oxidase-immobilized membrane recognized glucose and converted the chemical energy found in glucose to mechanical energy of actuation. The decompression unit of the system consisted of an enzyme co-immobilized dialysis membrane, an ultraviolet cross-linkable polymer of polyvinyl alcohol (PVA-SbQ), and polydimethylsiloxane (PDMS) microfluidic channels. According to the evaluation of the bonding condition between PVA-SbQ and PDMS, direct bonding with different polymer materials was realized without damage to the enzyme of glucose oxidase. The optimized plasma treatment conditions were a sweep rate of 400 mm/s and an applied electric power of 140 W. The decompression unit had an appropriate decompression rate (2.16 Pa/s) at the glucose concentration of the blood sugar level, which was achieved by increasing the enzyme membrane area per gas phase volume. The monolithic PDMS decompression unit is promising for the development of a chemo-mechanical device driven by human blood sugar for diabetes treatment in the future.