Hibifolin (HBF), a flavonol glycoside derived from herbal plants, possessed a strong protective activity against cell death induced by aggregated β–amyloid (Aβ). Therefore, detection of neuroprotective HBF in biological system of great significance for fundamental study in medicine field. To address this critical need, we herein developed a novel electrochemical sensor based on Zn–In2O3 nanorods coated glassy carbon microspheres paste electrode (Zn–In2O3NRs/GCPE) for HBF detection. Zn–In2O3NRs were successfully synthesized via a facile sol gel combustion method for the first time and assessed for their structural and morphological changes due to Zn doping into In2O3NPs by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The fabricated Zn–In2O3NRs/GCPE displayed high effective surface area, more reaction sites and excellent electrochemical catalytic activity toward the oxidation of neuroprotective HBF. Under the optimum conditions, the sensor showed fast and sensitive current response to HBF over a wide range of 1.95 × 10− 8–3.25 × 10− 6 M with a low detection limit of 3.10 × 10− 10 M (S/N = 3). Furthermore, this electrochemical sensor was successfully applied for the determination of HBF in spiked human biological fluids and in the flowers of hibiscus vitifolius with good accuracy and precision.