Immunosuppressive drugs are prescribed to reduce the immune system of persons who are undergoing organ transplants. The concentration of these drugs in blood and plasma samples must be accurately and precisely determined during immunosuppressive therapy due to their significant side effects. In this study, a metal organic framework-based dispersive solid phase extraction method was developed for the extraction of tacrolimus and cyclosporine from plasma samples before their determination by high performance liquid chromatography-tandem mass spectrometry. For this purpose, CuBTC metal organic framework nanoparticles were prepared by a hydrothermal approach and they were used as the sorbent in the extraction procedure. The adsorbed analytes were eluted by a suitable organic solvent and then more concentrated by evaporation of the eluate. All of the effective parameters of the method including sorbent amount, adsorption time, eluent type, desorption time, eluent volume, and sample solution pH were studied and optimized. They were obtained 5 mg, 5 min, acetone, 5 min, 300 μL, and 5, respectively. Under optimal conditions, the developed method was validated and the data showed that the linear range, the limit of detection, the limit of quantification, the coefficient of determination, the enrichment factor, and relative standard deviation values were 1-1000 ng mL-1, 0.30 ng mL-1, 0.5 ng mL-1, 0.99, 15.6, and 5.8 % for tacrolimus and 0.8-500 ng mL-1, 0.25 ng mL-1, 0.4 ng mL-1, 0.99, 17, and 5.6 % for cyclosporine, respectively. Finally, the method was successfully used in the determination of the studied drugs in plasma samples.