Nanoparticles containing silymarin derivatives were prepared from de-oiled silybum marianum seeds extract using supercritical CO2 (SC-CO2) and DMSO. All steps including lipophilic compounds removal, extraction, and particle production were carried out using SC-CO2. In This method, SC-CO2 was saturated with the solution of the extract at higher pressure. Then, depressurization of the supercritical solution led to a decrease in solvation power and particle formation while pressures at both conditions (pre-and post-expansion) were above the critical pressure. Characterization using LC-MS demonstrated that the extract and nanoparticles contained silymarin derivatives. Optimum conditions were obtained at a pressure of 350 bar, pressure drop of 230 bar, equilibration time of 30 min, collection time of 60 mirk, the extract volume of 20 mu L, and the temperature range of 55-60 degrees C. The average particle size was 70 +/- 20 nm at both conditions.