In this study, a new sensor for carbamazepine (CBZ) determination is designed. Graphitic carbon nitride (g-C3N4) -coupled with CuS nanoparticles exhibits an intensive fluorescence signal. Upon adding CBZ to the dispersed solution of g-C3N4@CuS resulted in the fluorescence quenching that can be used as a sensitive and selective chemical sensor for the quantitative determination of the CBZ. The photocatalytic performance of g-C3N4@CuS via CBZ degradation under visible light was also investigated. The removal efficiency of CBZ due to efficient photocatalytic degradation by g-C3N4 @ CuS was 98.5% under visible light illumination for 5h. This fluorescence sensor's behavior for quantitative sensing of CBZ was also examined, The effects of significant influencing variables, including pH, buffer types, buffer concentration, and dopant ratio were studied and optimized using response surface methodology (RSM). Under the optimum experimental conditions, the detection limit was 12.61 nM, and the linear range was 0 to 4.23 µM. This sensor showed many advantages, such as sensitivity, good selectivity, nontoxicity, simple operation, and low cost. The results showed the successful application in the determination of CBZ in human serum samples.