An innovative nanocomposite for the analysis of rosuvastatin (ROS) was constructed. The as synthesized nanocomposite composed of spinel copper ferrite nanoparticles (p-CuFeO2 NPs) supported on reduced graphene oxide (RGO) nanosheets in diethyl ammonium acid sulphate (DEAAS) as ionic liquid and anti-fouling agent. The prepared nanohybrid not only improves the interfacial electron transfer, but also readily exposed good catalytic effect toward ROS oxidation. The prepared sensor shows good oxidation behavior toward ROS oxidation in the range of 0.2–22.0 nM and the obtained LOD was 0.077 nM. To ensure good performance; the proposed sensor was used to determine ROS in different matrices and in human plasma. This study provides an efficient route to synthesize suitable nanohybrids for fabrication of potential sensors. Moreover, it opens new avenues in the manufacturing of ternary nanocomposite with excellent electrocatalytic effects.