Ag@rGO nanocomposite was prepared using an in situ reduction of silver ions and the as-synthesized graphite oxide (GO). Transmission electron microscopy analysis reveals a crumpled- and folded-layered structure of rGO with homogeneously dispersed spherical Ag NPs on these rGO nanosheets. The intensity ratio of the D to G bands (ID/IG) in Raman spectra for Ag@rGO indicates a large defect due to Ag NPs intercalation and deposition on rGO surface. X-ray diffraction indicates the face-centered cubic crystal structure of Ag with average crystalline size of 19.63 nm. An electrochemical sensor based on Ag@rGO is first designed for Prucalopride drug oxidation and characterized applying electrochemical impedance spectroscopy and cyclic voltammetry. Its electrocatalytic effect was enhanced upon utilizing a characterized activated charcoal (ACH) as an electro-modified carbon nanomaterial for CPE. The ternary nanocomposite [ACH/Ag@rGO] as a platform of CPE supposed three times higher response to Prucalopride compared to CPE. Prucalopride was quantified over wide linear ranges of (5.0×10-9–1×10-6 M) and (2.0×10-8–1.4×10-6 M), with LOD values of 7.95×10-10 M and 8.51×10-9 M in bulk form and spiked human plasma, respectively. This sensor can thus be adopted easily for quality control analysis of Prucalopride in formulation and human plasma and for pharmacokinetic study.