The fouling/wetting of hydrophobic membrane caused by organic substances with low-surface energy substantially limits the development of the membrane distillation (MD) process. The sulfate radical ()-based advanced oxidation process (AOP) has been a promising technology to degrade organics in wastewater treatment, and peroxydisulfate (PDS) could be efficiently activated by heat. Thus, a hybrid process of MD-AOP via PDS activated by a hot feed was hypothesized to mitigate membrane fouling/wetting. Experiments dealing with sodium dodecyl sulfate (SDS) containing a salty solution via two commercial membranes (PVDF and PTFE) were performed, and varying membrane wetting extents in the coupling process were discussed at different PDS concentrations and feed temperatures. Our results demonstrated permeate flux decline and a rise in conductivity due to membrane wetting by SDS, which was efficiently alleviated in the hybrid process rather than the standalone MD process. Moreover, such a mitigation was enhanced by a higher PDS concentration up to 5 mM and higher feed temperature. In addition, qualitative characterization on membrane coupons wetted by SDS was successfully performed using electrochemical impedance spectroscopy (EIS). The EIS results implied both types of hydrophobic membranes were protected from losing their hydrophobicity in the presence of PDS activation, agreeing with our initial hypothesis. This work could provide insight into future fouling/wetting control strategies for hydrophobic membranes and facilitate the development of an MD process.