Unmanned aerial vehicles (UAVs) are now very popular for many applications such as surveillance and transport and they are typically constructed starting from the design process. However, it is very time consuming and require all new airworthiness process. In this paper, we aim to provide a novel framework to automate an existing aircraft for unmanned operations using a humanoid robot, which is capable of manipulating the yoke, levers, switches and pedals to fly the airplane while operating various components such as lights and landing gears just as a human pilot would do. In this manner, the airplane can be converted for automated mode in a very short time without losing airworthiness. For testing, due to the complication of operating the robot in a real airplane, it is validated using a flight simulator, which provides the flight data over the network. The simulator is installed on a motion platform, which makes the robot move around due to the airplane’s motion for realism. The proposed method is successfully validated in a series of flight simulations with various scenarios to show the feasibility of humanoid robot operation of an aircraft under various conditions.