In recent years, obesity has become a major problem in the western world, affecting almost one-third of the population. Treatment for obesity is very expensive; therefore, the ‘fat-busting’ hormone leptin (LEP) has provoked wide-ranging interest over the last few years, and the immunosensing of LEP has received considerable attention in the field of obesity diagnosis. Bimetal oxides are significantly promising materials for biosensor applications owing to their large surface area, high stability, many active sites, and good biocompatibility. In this study, cerium niobate/cerium oxide (Ce3NbO7/CeO2) hollow nanospheres were synthesized using a template-free hydrothermal technique. The Ce3NbO7/CeO2 exhibits the high catalytic activity, large surface area, porous nature, and more active sites towards the LEP immunosensor. To improve the conductivity of the electrode, the AuNPs were decorated through the electrodeposition method (potential range: -0.4 to -0.9 V with an optimum successive cycle of 20). Au/Ce3NbO7/CeO2 was then thiol factionalized (Au-S bond-forming) with MPA to obtain a strong surface. Consequently, EDC/NHS enabled the −COOH group activation and firmly bonded with the anti-LEP molecules. Under optimal conditions, the developed immunosensor exhibited a good linear range from 0.5 pg/mL to 12,000 ± 500 pg/mL with a low detection limit (LOD) of 0.138 pg/mL, and good precision, selectivity, and stability results achieved for the immunosensing of LEP. Furthermore, the practical feasibility of LEP was demonstrated in plasma samples.