In this study, polystyrene nanofibers were prepared by electrospinning for the adsorption of olanzapine, risperidone, and clozapine from aqueous solution. The properties of polystyrene nanofibers were characterized via FTIR, SEM, TEM, TG, and XRD analyses. In addition, the impact of contact time, initial ion concentration, adsorbent dosage, temperature, and pH on the adsorption was studied. The adsorption kinetics and thermodynamic evaluation of three analytes on PS nanofibers were performed. The adsorption of the three analytes by polystyrene nanofibers followed the first-order kinetics with constant rates of 0.02348, 0.02683, and 0.03024 mg/g min for olanzapine, risperidone, and clozapine, respectively. Further, the adsorption conformed to Redlich-Peterson isotherm model and the maximum adsorption capacities for olanzapine, risperidone, and clozapine were 12.33, 8.36, and 12.96 mg/g, respectively. The adsorption process was characterized by spontaneous, exothermic, and physical reaction. The regeneration of nanofiber adsorbent showed that the adsorption capacity did not significantly change after 5 cycles of desorption. The selectivity of different analytes followed the order of clozapine > risperidone > olanzapine. Thus, the polystyrene electrospun nanofibers exhibit good potential as novel adsorbents for the isolation and purification of antipsychotic drugs from biological samples.