Origami structures are now applied more and more in industry with the advantages of enough stiffness to support weight, but can be folded flat for shipping or storage. Not only ordinary paper with small thickness 0.1mm, but also special paper materials such as cardboard or coated paper, which thickness is bigger (1–2mm) is used for forming origami structures. Therefore, the idea of designing an origami-performing robot to exclude human from folding the target work is now developed and investigated carefully. In this paper, we propose to develop a general simulation-based methodology for the manipulation with the paper origami structures as the basis for the robot design. Firstly, the problems of how to form the crease lines on the structure and the folding sequence on the different thickness of paper sheets by a robot hand are investigated carefully. Secondly, about the configuration of origami performing robot, we consider the reachability of manipulators, kinematics of the designed robot to extent the opportunities of application of robotics to fold the real origami structures in industrial and craft areas. Finally, with the purpose of using the robot for folding wide range of paper sizes’ formats and thickness, we suppose to minimize the size of the robotic system as much as possible to make it light weight and easy to use.