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, although DA suppressed the growth of A. erythraea, 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 both anaerobic and aerobic DA detoxification pathways in copepod gut bacteria, mediated by the genera Aureispira, Tenacibaculum, Pseudoalteromonas, Shewanella, and Vibrio. In the anaerobic pathway, DA could be biotransformed into detoxification products through a series of main degradation steps, including decarboxylation, dehydrogenation, carboxylation, and multiple β-oxidation processes. In the aerobic pathway, DA undergoes reactions including hydration, dehydrogenation, hydrolysis, hydroxylation, and oxidation, resulting in the formation of terminal detoxification products. 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.