In recent years, bionanomaterial-based electrochemical biosensor platforms have received much attention for the detection of various emerging biomarkers in the clinical, pharmaceutical, and biological fields. The integration of electrochemical systems with biomaterials, including proteins/enzymes, nucleic acids, and biopolymers, provides rapid, sensitive and selective detection of biomarkers. This review discusses the development of biomaterial-derived electrochemical sensors and biosensor platforms for the next generation of medical diagnosis and real-time monitoring of the clinical status of patients at various levels. The complete utilization of various bionanomaterials and their nanocomposites in the design of high-performance electrochemical biosensor platforms for the sensitive and selective detection of emergent biomarkers will be described. Moreover, the prominent opportunities for designing biomaterials and analytical strategies to improve the performance of biosensors via multi-label intensification integrated with high volumes of capture molecules on material surfaces for further advances in biomedical fields will be discussed.