Nowadays, the ubiquity of smart appliances in our everyday lives is increasingly strengthening the links between humans and machines. Beyond making our lives easier and more convenient, smart devices are now playing an important role in personalized healthcare delivery. This technological breakthrough is particularly relevant in a world where population aging and unhealthy habits have made non-communicable diseases the first leading cause of death worldwide according to international public health organizations. In this context, smart health monitoring systems termed Wireless Body Sensor Nodes (WBSNs), represent a paradigm shift in the healthcare landscape by greatly lowering the cost of long-term monitoring of chronic diseases, as well as improving patients' lifestyles. WBSNs are able to autonomously acquire biological signals and embed on-node Digital Signal Processing (DSP) capabilities to deliver clinically-accurate health diagnoses in real-time, even outside of a hospital environment. Energy efficiency and reliability are fundamental requirements for WBSNs, since they must operate for extended periods of time, while relying on compact batteries. These constraints, in turn, impose carefully designed hardware and software architectures for hosting the execution of complex biomedical applications. In this thesis, I develop and explore novel solutions at the architectural and technological level of the integrated circuit design domain, to enhance the energy efficiency and reliability of current WBSNs. Firstly, following a top-down approach driven by the characteristics of biomedical algorithms, I perform an architectural exploration of a heterogeneous and reconfigurable computing platform devoted to bio-signal analysis. By interfacing a shared Coarse-Grained Reconfigurable Array (CGRA) accelerator, this domain-specific platform can achieve higher performance and energy savings, beyond the capabilities offered by a baseline multi-processor system. More precisely, I propose three CGRA architectures, each contributing differently to the maximization of the application parallelization. The proposed Single, Multi and Interleaved-Datapath CGRA designs allow the developed platform to achieve substantial energy savings of up to 37%, when executing complex biomedical applications, with respect to a multi-core-only platform. Secondly, I investigate how the modeling of technology reliability issues in logic and memory components can be exploited to adequately adjust the frequency and supply voltage of a circuit, with the aim of optimizing its computing performance and energy efficiency. To this end, I propose a novel framework for workload-dependent Bias Temperature Instability (BTI) impact analysis on biomedical application results quality. Remarkably, the framework is able to determine the range of safe circuit operating frequencies without introducing worst-case guard bands. Experiments highlight the possibility to safely raise the frequency up to 101% above the maximum obtained with the classical static timing analysis. Finally, through the study of several well-known biomedical algorithms, I propose an approach allowing energy savings by dynamically and unequally protecting an under-powered data memory in a new way compared to regular error protection schemes. This solution relies on the Dynamic eRror compEnsation And Masking (DREAM) technique that reduces by approximately 21% the energy consumed by traditional error correction codes.