The article reviews the progress and opportunities in the development of electrochemical protein biosensors for disease marker detection. It highlights the challenges and advancements in sensor sensitivity and practical application, emphasizing the role of electrode-modified materials and transducer devices. The review covers recent reports on electrochemical biosensors for detecting cancer, viral infectious diseases, inflammation, and other diseases, detailing the corresponding sensitive materials, transducer structures, and detection principles. The article also presents an outlook on the future trends in the development of electrochemical protein biosensors for disease biomarker detection, including the use of nanomaterials, nanoenzymes, and wearable systems.The article reviews the progress and opportunities in the development of electrochemical protein biosensors for disease marker detection. It highlights the challenges and advancements in sensor sensitivity and practical application, emphasizing the role of electrode-modified materials and transducer devices. The review covers recent reports on electrochemical biosensors for detecting cancer, viral infectious diseases, inflammation, and other diseases, detailing the corresponding sensitive materials, transducer structures, and detection principles. The article also presents an outlook on the future trends in the development of electrochemical protein biosensors for disease biomarker detection, including the use of nanomaterials, nanoenzymes, and wearable systems.