Domoic acid (DA) is a neurotoxin produced by certain species of Pseudo-nitzschia (PSN) that can cause damage to neural tissues and can be fatal to marine animals. Copepods, direct consumers of PSN, exhibit remarkable resistance to DA. Given that gut microbiota facilitate various detoxification processes in copepods, we hypothesize that gut microbiota may play a crucial role in aiding copepods in DA detoxification. In this study, we investigated the detoxification capability of copepod gut microbiota by feeding both wild-type and gut-microbiota-free Acartia erythraea toxic PSN. Our results demonstrated that the presence of gut microbiota enhanced the survival of copepods exposed to a DA diet. We subsequently feed A. erythraea both toxic and non-toxic PSN, and explored the potential mechanisms of DA detoxification through amplicon and metatranscriptome approaches. We identified Aureispira sp., Oceanospirillum sp., and Tenacibaculum sp. as key DA detoxification taxa because they not only exhibited high relative abundance in the toxic diet but also played an important role in two established DA biotransformation pathways. We speculate that the gut microbiota of A. erythraea transform DA into non-toxic substances through these two established pathways via decarboxylation, dehydrogenation, carboxylation, and multiple oxidation processes. Overall, our findings elucidate the mechanisms by which copepod gut microbiota detoxify DA, thereby advancing our understanding of copepod resilience in the face of a toxic diet.