Glutamate is one of the most prominent neurotransmitters in mammalian brains, which plays an important role in neuronal excitation. High levels of neurotransmitter cause numerous alterations, such as calcium overload and the dysfunction of mitochondrial and oxidative stress. These alterations may lead to excitotoxicity and may trigger multiple neuronal diseases, such as Alzheimer's disease, stroke, and epilepsy. Excitotoxicity is a pathological process that damages nerve cells and kills cells via excessive stimulation by neurotransmitters. Monitoring the concentration level of brain glutamate via an implantable microbiosensor is a promising alternative approach to closely investigate in the function of glutamate as a neurotransmitter. This review outlines glutamate microbiosensor designs to enhance the sensitivity of glutamate detection with less biofouling occurrence and minimal detection of interference species. There are many challenges in the development of a reproducible and stable implantable microbiosensor because many factors and limitations may affect the detection performance. However, the incorporation of multiple scales is needed to address the basic issues and combinations across the various disciplines needed to achieve the success of the system to overcome the challenges in the development of an implantable glutamate biosensor.