Electrochemical biosensors are essential tools with wide-ranging applications that significantly enhance the lives of patients suffering from complex metabolic diseases, as well as aid in the diagnosis of biomolecules and viruses. This discussion begins with an overview of the evolution of electrochemical biosensors, highlighting the different generations of these technologies. In terms of design, the choice of critical nanomaterials is vital, particularly focusing on the properties of 2D materials such as graphene and the techniques used for their functionalization. Additionally, this discussion includes graphene-based electrochemical biosensors and graphene quantum dot fluorescence biosensors that have been developed for detecting glucose molecules, drawing from the author’s previous work. Special attention is given to the broader impact of graphene in the detection of COVID-19, examining various types of biosensors, including electrochemical, field-effect transistor, and plasmon resonance methods. Finally, the progress of smart glucose sensors is explored, particularly implantable, wearable, and minimally invasive glucose biosensors that are integrated with smart devices, such as watches and mobile phones, to facilitate data acquisition. This serves as a prospective outlook for the future of biosensors.