The human-centered technology in smart manufacturing has been considered as the new generation technology to serve intelligent, green manufacturing systems, also known as human-cyber-physical systems. The human digital twin strategy provides a manufacturing system with cutting-edge technology to achieve human–machine interaction in real time and unmanned work environment for the safety consideration. This chapter comprehensively describes the essential role of humans in manufacturing activities and systematically reviews the research advances on human digital twins. Addressing the issues of safety, human–machine–environment interaction, and health monitoring in the manufacturing process, a human skeleton digital twin framework is proposed for the human behaviors-oriented in the manufacturing process based on predictive modeling technologies. The feasibility and effectiveness of the proposed framework are verified by using a medical image-based human lumbar spine model during manufacturing process, which exhibits how the human–machine dynamic interactions work in the manufacturing process and how the biomechanical features of human skeleton are detected in real-time during the manufacturing process. Several proposals on model construction, data collection, and production service, are present for addressing the issues and challenges in the human digital twin.