In this study, a forward osmosis coupled with electrochemical oxidation (FO-EO) process was used to achieve simultaneous rejection and degradation of 15 pharmaceutically active compounds (PhACs) in wastewater. The influence of wastewater effluent organic matter (EfOM) on PhACs removal was investigated. Sodium alginate (SA), humic acid (HA) and bovine serum albumin (BSA) were used as model organics to represent major constituents of EfOM. Results demonstrated that a generally negative influence of SA on PhACs rejection was observed due to membrane fouling in FO processes. During FO-EO processes, high rejection ( > 95%) and degradation efficiencies ( > 94%) of 15 PhACs were achieved simultaneously. With the presence of model organics in feed, adverse impacts on PhACs degradation were observed in the order of HA > BSA > SA. Results of UV and EEM fluorescence spectroscopy detection verified the competition of EfOM with PhACs for electrochemical oxidation, further proving the role of natural organic matter (NOM) and proteins in impeding the PhACs removal in FO-EO processes. Moreover, degradation products of PhACs were identified. And the acute toxicity of the feed was decreased after treated by FO-EO processes although the mineralization of PhACs was partially achieved. Furthermore, PhACs in actual secondary effluent were well removed by FO-EO processes, exhibiting a desirable application performance.