The goal of this research is the development of multiple monolithic fiber-solid phase microextraction (MMF-SPME) using a new integrated fiber for the determination of amphetamine derivatives and modafinil from unauthorized medicinal supplements. For this purpose, a monolithic fiber of metal organic framework MIL-Al (53)-deep eutectic solvent (DES)/molecularly imprinted polymers (MOF-DES/MIP) was synthesized. To find optimum microextraction conditions gas chromatography-mass spectrometer (GC-MS) was used and the influences of effective variables were investigated using one factor at a time method. After that, the significant variables were optimized using a Box-Behnken design (BBD) combined with a desirability function (DF). Under optimized conditions (desorption solvent=1500 µL of 1-octanol, pH=3.5, extraction time=35 min, [NaCl]=0% w/v and stirring rate=600 rpm), calibration graphs of analytes were linear in a concentration range of 0.1–400 μg L−1 with correlation coefficients > 0.9966. Limits of detection and quantification were in the ranges of 0.023–0.033 μg L−1 and 0.088–0.113 μg L−1, respectively. This procedure was successfully employed in determining target analytes in spiked and unspiked unauthorized medicinal supplement samples with recoveries ranging from 95.14 to 104.63%.