Supercritical extraction is powerful new technique in sepration processes and environmentally is more appropriate than crystallization, adsorption, chromatography and evaporation methods. Crocin and safranal are two active constituents of saffron and remedial for different disease especially Alzheimer's disease. In this study, crocin was extracted via supercritical carbon dioxide (SC-CO 2 ) with methanol as an entrainer and safranal was extracted via supercritical carbon dioxide and Subsequently the results were compared with Soxhlet method as the base case of 100% recovery. The extracted samples were analyzed by high performance liquid chromatography (HPLC) and Response surface methodology was employed to optimize the extraction parameters. The crocin and safranal recovery results indicated that the data adequately fitted into a second-order polynomial model.R 2 and modified R 2 of the model are 97.11% and 94.58%, for crocin and 97.52%, 95.35% for safranal respectively. It was predicted that the optimum extraction conditions within the experimental ranges would be the extraction pressure of 19.3MPa, temperature of 43.9 o C, flow rate of 1.0 ml/min, and exraction time of 110.0 min with recovery 32.67 w/w%. and the safranal recovery results indicated that the maximum recovery of 91.76 w/w% was obtained at optimal operating conditions of 92.4 o C, 21.3 MPa, 0.87 mL/min and 122.0 min (dynamic extraction time). Moreover, in the present study, a mathematical modeling for extraction of crocin and safranal from saffron using supercritical carbon dioxide was performed. Finally these were optimized by genetic algorithm,that was obvious good agreement between two methods of optimization. (genetic algorithm and RSM) Key Words Saffron, Crocin, Safranl, Alzheimer, HPLC , Supercritical extraction, Co-solvent, Response surface methodology, Mathematical modeling, Genetic algorithm.