<p>Graphene-based nanoelectronic biosensors have emerged as transformative platforms for early disease detection due to their exceptional electrical conductivity, high carrier mobility, and large surface-to-volume ratio enabling ultra-sensitive biomolecular interactions. This review critically examines the integration of graphene and its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), into advanced biosensing systems, emphasizing structure–property relationships governing analytical performance. Key device configurations, including field-effect transistors (FETs), electrochemical sensors, and optical platforms, are analyzed, demonstrating detection limits ranging from femtomolar to attomolar levels depending on sensor architecture, target biomarker, and sensing conditions, with rapid response times under optimized conditions. Surface functionalization strategies such as covalent modification and π–π stacking are highlighted for improving selectivity toward proteins, nucleic acids, and small-molecule biomarkers while reducing nonspecific interactions. Applications across oncology, infectious diseases, and neurodegenerative disorders illustrate multiplexed detection and clinically relevant sensitivity. Compared to conventional systems, graphene-enabled biosensors exhibit superior signal-to-noise ratios and real-time monitoring capabilities in complex biological environments. Challenges including reproducibility, long-term stability, and scalable fabrication are discussed, along with emerging solutions involving hybrid nanomaterials and microfluidic integration. The review concludes with a translational perspective on point-of-care and wearable biosensing technologies, highlighting graphene nanoelectronics as a key driver of precision diagnostics.</p> Graphical abstract <p></p>