The sensing of glucose can be divided into enzymatic glucose sensing and non-enzymatic glucose sensing based on the sensing mechanisms. The differentiation between non-enzymatic and enzymatic techniques is based on the electrooxidation reaction of glucose molecules. In nonenzymatic techniques, this reaction occurs directly, while in enzymatic techniques, the reaction is indirect. Both techniques have their advantages and disadvantages, and researchers continue to explore ways to improve glucose sensing in the clinical setting. Significant progress has been made in the field of commercial electrochemical glucose biosensors due to advancements in surface chemistry and device fabrication. Researchers have explored a variety of inorganic redox couples and mediators, such as methylene blue, ferricyanide, ferrocene, and methyl viologen, to transport electrons from the enzyme to the working electrode surface. Among these mediators, ferrocene is commonly used because of its fast reaction with the enzyme, wide range of pH settings, and reversible electron kinetics. Second-generation glucose sensors, utilizing a redox couple or mediator-based approach, have outperformed first-generation sensors since 1984 due to their sensitivity to dissolved oxygen, even at lower potentials and extreme interference ambience. The commercial product was made possible by the discovery of a screen-printing process that enabled the creation of wearable, disposable, compact, and pocket-friendly electrodes. Each test strip contains miniaturized screen-printed electrodes, with the working electrode coated with the functional sensing components, including an electron-shuttle redox mediator, glucose oxidase linking agent, and stabilizer. Despite ongoing debates about the relevance of second-generation glucose detectors, these developments have had a tremendous impact on glucose sensing and monitoring.