The development of crystal-facet metal oxide heterostructures has been of great interest owing to their rational design and multifunctional properties at the nanoscale level. Herein, we report a facile solution-based method for the synthesis of single-crystal Cu2O nanostructures (i.e. Cu2O-CuO) as a core. Graphene quantum dots (GQDs) with varying concentrations are fabricated on the surface of Cu2O extended hexapods (EHPs) in ethanol solution at room temperature via self-assembly, where copper acts as a sacrificial model and a stabilizer as well. The Cu2O crystals displayed a good sensing activity toward BPA oxidation owing to their high energy facets, dangling bonds and great proportion of surface copper atoms. Structural, morphological, chemical and vibrational investigations were performed in detail, presenting high crystallinity of hybrid nanocomposites and Cu2O-CuO heterojunction positions along with the growth of GQDs on the core of Cu2O-CuO crystals. The electrochemical sensing performance of the as-fabricated Cu2O-CuO@GQD EHPs was monitored for the determination of bisphenol A (BPA) as an early diagnostic marker and environmental contaminant. The synergistic effects of the boosted surface area, exposed Cu {111} crystallographic planes and mixed copper valences enhance redox reaction kinetics by increasing the electron shuttling rate at the electrode-analyte junction. Benefitting from the improved electrocatalytic activity for BPA oxidation, the electrochemical sensor displayed the lowest limit of detection (≤1 nM), good chemical stability, a broad linear range (2 nM-11 mM), and high sensitivity (636 μA mM-1 cm-2). The Cu2O-CuO@GQD EHP-based sensing platform was used for BPA detection in water and human serum samples. We have also constructed a pioneering electrochemical sensing platform for BPA detection in live cells, which might be used as a marker for early disease diagnosis.