Diabetes mellitus (DM) is a global health problem leading to many complications and disabilities in life adjusting activities and even dead. Monitoring glucose levels is a key factor in diagnosis and management of DM. Conventional glucose sensors consisted of immobilized enzymes, are so susceptible to environmental conditions. In this way, nonenzymatic biosensors have attracted extensive attentions in many clinical diagnostics applications. To date, the finger pricking test is a common enzyme-based glucometer that is an invasive and inconvenient and may lead to infections in the injection sites. So, working on the possibility of cutaneous or subcutaneous insertion of devices as a noninvasive or minimally-invasive systems for continuous glucose controlling approaches through human biofluids (blood, perspiration, tears, saliva, etc.) have stimulated growing interest. This review summarizes recent nonenzymatic and noninvasive biofluids glucose monitoring systems which are highly resilience and stretchable to continuously adapt to body movements during common physical activity. Sensors are based on their constituent materials including carbon-based, metal nanoparticles, polymer, and hydrogel systems are classified for electrochemical, and optical glucose detection. Finally, we address the drawbacks and challenges of enzyme-free sensors which are aroused sustaining research passion to be used in point-of-care medical diagnostics applications.
