The integration of flexible and nanostructured electronics into neuroscience is transforming how we interface with neural tissue, particularly glial cells, which play crucial roles in neurophysiology, neuroprotection, and neuroinflammation. Unlike traditional rigid bioelectronic devices, flexible and nanostructured materials provide improved mechanical compliance, enhanced biocompatibility, and superior signal transduction, making them ideal for long-term neural interfacing. This chapter explores the development, materials, fabrication techniques, and biological considerations of microelectrode arrays (MEAs) designed for communication with glial cells. The chapter begins with an overview of flexible electronics, describing their key properties and advantages in biomedical applications. The role of flexible materials in neural interfacing is examined, highlighting their capacity to accommodate the mechanical properties of biological tissue while minimizing inflammatory responses. Their applications in medical devices and neuroscience, particularly in the context of chronic neural recording, brain–machine interfaces, are also addressed. The chapter then focuses on microelectrode arrays (MEAs), one of the main tools used for electrophysiology, detailing the materials utilized for electrode fabrication, including metallic (e.g. gold, platinum, iridium), metal oxide (e.g. indium tin oxide, ruthenium oxide), and conductive polymer-based electrodes (e.g. PEDOT:PSS). Structural modifications such as nanostructured surfaces and bioactive coatings are explored due to their role in enhancing cell adhesion, reducing impedance, and improving signal transduction. The selection of flexible substrate materials, including polyimide, parylene-C, and hydrogels, is analysed in relation to their mechanical and electrical properties in biological environments. Microfabrication techniques relevant to MEAs are discussed, differentiating between top-down approaches (e.g. photolithography, etching) and bottom-up methods (e.g. self-assembly, chemical vapor deposition). The influence of these fabrication techniques on nanostructured electrode design is highlighted, particularly in relation to optimizing interactions between electrodes and glial cells. A detailed examination of the biological interface between MEAs and glial cells, including astrocytes and their role in the tripartite synapse, is provided. The impact of glial scarring, a major challenge for long-term neural interfaces, is considered alongside strategies for its mitigation, including the use of biomimetic coatings, anti-inflammatory surface treatments, and nanostructured modifications. Further analysis is given to the effect of electrode architectures—specifically ordered versus disordered nanostructures—on cellular interactions, with implications for signal fidelity and long-term stability. The final sections address signal recording methodologies, with a focus on how nanostructured flexible electrodes contribute to improved sensitivity, spatial resolution, and long-term stability in neural interfacing. Recent innovations in low-noise recording systems, impedance matching, and real-time signal processing are reviewed to illustrate advances in neural data acquisition. Concluding remarks outline future directions in the development of flexible and nanostructured neuro and glioelectronic platforms. Emerging technologies, including biohybrid interfaces, neuromorphic electronics, and optogenetically integrated electrode systems, are highlighted as potential strategies for enhancing neural communication. The continued refinement of these bioelectronic interfaces is expected to contribute to the advancement of neuroscience, particularly in the context of long-term interactions with glial cells and neural networks.