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Microplastics (MPs)/nanoplastics (NPs) have been widely detected in wastewater treatment plants (WWTPs). They are captured mainly by sludge and unavoidably move into the anaerobic digestion (AD) process. Recent studies suggested that MPs/NPs could induce oxidative stress to the microbiome in digesters. The thermal hydrolysis process (THP) has been implemented for sludge pretreatment in many full-scale WWTPs. To date, there is limited knowledge about how THP can influence MPs/NPs-induced stress during AD. This study systematically investigated the impact of THP (80 and 160 °C) on AD of sewage sludge exposed to different levels (50–150 μg/L) of polystyrene nanoplastics (PsNPs), one of the most found MPs/NPs in WWTPs. Compared to the control, higher PsNPs levels of 100 and 150 μg/L decreased methane yields by 17.98 and 29.34%, respectively. Moreover, reactive oxygen species (ROS) levels increased by 17.18 and 34.84%. Our results demonstrated that THP counteracted the suppression of methane production imposed by such PsNPs concentrations, with decreased ROS levels. Also, THP reduced antibiotic resistance gene (ARG) propagation that can be encouraged by PsNPs, thus minimizing the ARG transmission risks of digestate biosolids. These findings suggest that THP holds a high promise to further develop as a remediation method for MPs/NPs in WWTPs.