Domoic acid (DA) is a shellfish neurotoxin mainly produced by the diatoms of some species of Pseudo-nitzschia and Nitzschia in the ocean. To date, most reports on DA have focused on its effects on mice, humans, birds, and other animals, and have revealed that DA causes neurotoxicity in mammals. Although some studies on invertebrates have been reported, most have only reported the concentration of DA in various tissues of shellfish, which are important top predators. Few studies have reported the toxicological effects of DA on the shellfish themselves. Scallops, as invertebrates, lack adaptive immunity and mainly rely on an innate immune system for defense. Acid phosphatase (ACP) and lysozyme (LZM) are important lysosomal enzymes that are involved in humoral immune responses. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions into H₂O₂ and O₂^- (disproportionation) to prevent lipid peroxidation. This process plays a very important role in biological defense. Glutathione, as an antioxidant, exhibits antioxidant effects by scavenging reactive oxygen species and protecting the sulfhydryl (-SH) group in bio-macromolecules. Glutathione S-transferase (GST) can catalyze the binding of GSH to electrophilic intermediate metabolites, thus reducing the toxicity associated with endogenous or exogenous poisons. This process plays an important role in the detoxification system. Therefore, in this study, in order to reveal DA exposure-induced toxicity on the immune and antioxidant system of scallops, the bay scallop (Argopecten irradians) was exposed to different concentrations (0, 10, 50, and 100 ng/mL) of DA and the SOD activity and GSH content in its hemolymph, and the relative expression levels of related genes (Cu/ZnSOD, MnSOD, GST, and ACP), were measured. The results showed that LZM activity significantly increased in the 10 and 50 ng/mL DA-treatment groups. The expression of ACP was upregulated at 6 and 12 h and was significantly downregulated at 24 h. These results suggest that low and medium concentrations of DA could momentarily stimulate the immune responses of the bay scallop. However, SOD activity was inhibited after exposure to 10, 50, and 100 ng/mL of DA (6-24 h exposure), and the relative mRNA expression of Cu/ZnSOD and MnSOD were also regulated. DA may inhibit SOD activity and affect it by disturbing the related mRNA expression at the gene level. Moreover, the GSH content significantly increased, and GST was significantly upregulated following DA exposure, indicating that the glutathione system was involved in resistance against DA toxicity. Generally, DA exposure could inhibit SOD activity. Short-term treatment with a lower concentration can stimulate the immune responses, while long-term treatment at high concentrations would cause immune fatigue. However, the bay scallop could resist the toxicity of DA by increasing the level of GSH in its hemolymph and by expressing GST. Thus, this study preliminarily revealed the effects of DA on immunity, antioxidant capacity, and the detoxification mechanisms of bivalves such as scallops.