A SiC-nanoparticles modified glassy carbon electrode has been used for the determination of nimesulide (NIME) in drug formulations and human serum by differential pulse voltammetry. Nimesulide, chemically (N-(4-nitro-2-phenoxyphenyl)-methane-sulphonamide) is a relatively new non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties, which does not induce gastrointestinal ulceration. NIME is a methanesulphonic acid anilide derivative. For the determination of NIME in drugs and biological samples separation (about 65%), spectrophotometric (about 26%) and electroanalytical (about 9%) methods are used. Most of all the applications, HPLC with spectrophotometry, MS and electrochemical detection were described. Electrochemical techniques are suitable in samples containing complex matrix such as syrups, tablets, creams or biological fluids. The purpose of this work is to investigate the differential pulse voltammetry (DPV) behavior of NIME using SiC-nanoparticle modified GCE. Compared to a bare GCE the SiC-nanoparticle modified electrode exhibited a marked enhancement in the current response of NIME. The effect of pH and apparatus parameters such as interval time, modulation time, step potential and amplitude were optimized. The calibration plot having good co-linearity with a correlation coefficient 0.9925 was obtained in the concentration range of 0.08-7.0 µg mL-1 NIME. The detection limit (S/N = 3) of NIME in the standard solution (pH 2.0) is estimated to be 0.03 µg mL-1. The low-cost modified electrode showed good sensitivity, selectivity, stability and had been applied to the determination of nimesulide in pharmaceutical formulation and human serum samples without any preliminary treatment, with satisfactory results.