Today, historic villages represent a widespread and relevant reality of the Italian administrative structure. To preserve their value for future generations, smart city applications can contribute to implement effective monitoring and decision-making processes devoted to safeguarding their fragile ecosystem. Starting from a situational awareness model, this study proposes a method for designing human-in-the-loop cyber-physical systems that allow the design of monitoring and decision-making applications for historic villages. Both the model and the design method can be used as a reference for the realization of human-in-the-loop cyber-physical systems that consist of human beings, smart objects, edge devices, and cloud components in edge-cloud architectures. The output of the research, consisting of the graphical models for the definition of monitoring architectures and the method for the design of human-in-the-loop cyber-physical systems, was validated in the context of the village of Sant’Agata dei Goti through the implementation of a human-in-the-loop cyber-physical system for monitoring sites aiming at their management, conservation, protection, and fruition.