Although there is increasing concern about the toxicity of nanoplastics, the effects of nanoplastic exposure and subsequent recovery on immune responses, as well as antioxidant responses and gut microbiota, in crustaceans are rarely reported. In this study, the nonspecific immunity and antioxidant defense of Eriocheir sinensis were evaluated after acute exposure to various concentrations (0, 2.5, 5, 10 and 20 mg/L) of 75-nm polystyrene nanoplastics (PS-NPs) for 48 h, as well as after 7 days of recovery from the nanoplastic environment. The results showed that, after 48 h of exposure, nanoplastics were observed in the gills, hepatopancreas and gut. However, no nanoplastics were found in the gut after 7 days of recovery. Under nanoplastic-induced stress, Hc, Relish, proPO, and LITAF mRNA levels increased in the gills and hepatopancreas for 48 h. Expression of the myd88, Hc, Relish and proPO genes decreased in the gills during the 7-day recovery period. Exposure to nanoplastics for 48 h and recovery for 7 days significantly decreased the activities of lysozyme (LZM) alkaline phosphatase (AKP), total superoxide dismutase (SOD) and phenoloxidase (POD) and, glutathione peroxidase (GPX) in the hepatopancreas. Meanwhile, the relative abundance of pathogens exposed to 10 mg/L nanoplastics for 48 h increased at the species level, and these pathogens decreased significantly in the 7-day recovery period. These results suggested that exposure to nanoplastics for 48 h affected the activities of immune system enzymes and expression of immune-related genes in Eriocheir sinensis and altered the diversity and composition of their gut microbiota. E. sinensis could not recover from damage to the hepatopancreas within a 7-day recovery period. The results of this study provided insight into the effects of nanoplastics on crustaceans and it filled a gap in research on crustacean recovery after exposure to nanoplastics.