Smart biosensors attract significant interest due to real‐time monitoring of user health status, in which bioanalytical electronic devices designed to detect and track various activities and biomarkers in the human body have potential applications in physical sign monitoring and health care. Bioelectronics can also be well integrated by output signals with wireless communication modules for transferring data to portable devices used as smart biosensors in performing real‐time diagnosis and analysis. In this review, the scientific keys of bio‐sensing devices and the current trends in the field of smart biosensors, i.e., functional materials, technological approaches, readout circuits, sensing mechanisms, main roles, potential applications in health monitoring, and challenges in future works, will be summarized and highlighted. Recent advances in the design and manufacturing of bioanalytical sensors with smarter capabilities and enhanced reliability indicate a forthcoming expansion of these smart electronic devices from lab to clinical analysis. Therefore, a general description of functional materials and technological approaches used in bioelectronics will be presented after the sections of scientific keys to bioanalytical sensors. A careful introduction to the established systems of smart monitoring and prediction analysis using bioelectronics, regarding the integration of machine‐learning‐based basic algorithms, will be discussed. Afterward, potential applications and challenges in development using these smart bioelectronics in biological, clinical, and medical diagnostics will also be analyzed. Finally, the review will conclude with outlooks of smart bio‐sensing devices assisted by machine learning algorithms, wireless communications, or smartphone‐based systems on current trends and challenges for future works in wearable health monitoring.This article is protected by copyright. All rights reserved