In the last decade, we have witnessed the rapid development of electronic technologies that are transforming our daily lives. Such technologies are often integrated with various sensors that facilitate the collection of human motion and physiological data and are equipped with wireless communication modules such as Bluetooth, radio frequency identification, and near-field communication. In smart healthcare applications, designing ergonomic and intuitive human-computer interfaces is crucial because a system that is not easy to use will create a huge obstacle to adoption and may significantly reduce the efficacy of the solution. Signal and data processing is another important consideration in smart healthcare applications because it must ensure high accuracy with a high level of confidence in order for the applications to be useful for clinicians in making diagnosis and treatment decisions. This Special Issue is a collection of 10 articles selected from a total of 26 contributions. These contributions span the areas of signal processing and smart healthcare systems mostly contributed by authors from Europe, including Italy, Spain, France, Portugal, Romania, Sweden, and Netherlands. Authors from China, Korea, Taiwan, Indonesia, and Ecuador are also included.