The supercritical carbon dioxide-assisted extraction (SC $CO_2E$) process was optimized for extracting picroside I and picroside II from Picrorhiza scrophulariiflora rhizomes. The picroside I and picroside II content was determined using validated LC-MS methodology. The response surface methodology (RSM) was employed to study quantitative effects of extraction parameters viz. operating pressure, temperature, modifier concentration and extraction time using Box-Behnken design. The experimental data were fitted to second-order polynomial equation using multiple regression analysis and analyzed using the appropriate statistical method. By solving the regression equation and analyzing 3D plots, the optimum extraction conditions were found to be: extraction pressure, 25 MPa; temperature, $40^{circ}C$; modifier concentration, 15 % and extraction time, 90 min. The effect of four different ionic liquids (IL) as a modifier additive has been investigated using optimized SC $CO_2E$ conditions. None of the IL showed equivalent or enhanced recovery of analytes of interest. The conventional hot percolation of P. scrophulariiflora powder resulted in $23.69{pm}1.02$ and $10.22{pm}0.71mg;g^{-1}$ picroside I and II, respectively, after an extraction period of 6 h whereas SC $CO_2E$ with methanol as modifier showed $33.14{pm}1.23$ and $16.77{pm}0.82mg;g^{-1}$ recovery of picroside I and II, respectively in 90 min. The comparison of yield and extraction time demonstrated that SC $CO_2E$ using methanol as modifier is more efficient than conventional hot percolation method.