Digital tools are notoriously able to assist designers in solving several issues with high accuracy and minimized computational efforts. In this sense, maximization of human comfort in the built environment is a target for various design procedures, where mathematical models and standardized protocols are generally used for well-being purposes. In this paper, a selection of recent experimental studies and pilot studies in which various artificial intelligence tools and wearable or smartphone-based sensors are used to support a rapid and efficient body motion analysis are used to support and assess a multi-criteria human comfort-driven design approach for various structural building components and configurations of technical interest. The so-called “emotional architecture” and its correlated nervous feelings, as well as human reactions and behaviours, which are intrinsic part of the issue, are quantitatively measured and compared to find possible feedback in structural design optimization. Major modification in human behaviours can result in relevant changes of body motion features, and thus in corresponding reaction forces, loading conditions, operational configurations for structural components and systems, etc. Both remote digital technologies based on artificial intelligence and facial micro-expression analysis, as well as multiple wearable or smartphone-based sensors are used for in-field experiments, to capture kinematic and biometric parameters of volunteers moving in various structural environments, are summarized in this paper. Trends and challenges of these applications are discussed with practical examples.