A simulation device of an entire natural gas hydrate exploitation process includes a high pressure reaction kettle, a gas-liquid separation device, a hydrate accumulation simulation subsystem simulating a hydrate accumulation process, a hydrate formation drilling simulation subsystem simulating a hydrate formation drilling process, a hydrate exploitation simulation subsystem simulating a hydrate decomposition and gas production process, and a produced gas collecting and processing simulation subsystem simulating a produced gas collecting and processing process. A method for simulating an entire natural gas hydrate exploitation process includes a hydrate accumulation process, a hydrate formation drilling process, a hydrate exploitation process and a produced gas collecting and processing process. With this simulation device and method, the external environment can be truly simulated, so that the authenticity and accuracy are better, and the entire natural gas hydrate exploitation process is continuously simulated and comprehensively evaluated to provide guidance for natural gas hydrate exploitation.