Abstract: This research evaluated the impacts of various soybean-derived protein sources on growth performance, hepatopancreatic damage, and intestinal microbial profiles in red swamp crayfish (Procambarus clarkii). Four isonitrogenous and isolipidic diets were formulated: a basal diet containing 20% fishmeal (FM), and three diets replacing fishmeal with soybean meal (SBM), fermented soybean meal (FSM), and soybean protein concentrate (SPC). Six hundred crayfish initial weight (4.00±0.50) g were randomly divided into four groups with three biological replicates each, and fed for 6 weeks. The results showed that weight gain rate (WGR) and specific growth rate (SGR) in the SBM group were significantly lower than those of the FM group (P<0.05). Conversely, the WGR and SGR of the FSM and SPC groups were significantly higher than those of the SBM group (P<0.05). Compared to the FM group, crayfish fed SBM diet exhibited ruptured basement membranes of hepatic tubules, along with significant increases in the activities of GOT and GPT in the hemolymph (P<0.05). Moreover, the activities of CAT, SOD, and GPx, as well as the content of GSH in the hepatopancreas, were significantly decreased (P<0.05), while the activity of GR and the content of MDA increased significantly (P<0.05). Compared to the SBM group, GR activity and MDA content in the hepatopancreas in the FSM and SPC groups were significantly lower (P<0.05), and CAT activity in the FSM increased significantly (P<0.05). Compared to the FM group, SBM feeding trended toward upregulated nfkb and tlr mRNA expression and downregulated lzm mRNA expression in the hepatopancreas. In contrast, FSM and SPC groups showed decreased nfkb and tlr expression and increased lzm expression relative to SBM. The relative abundance of Anaerorhabdus furcosa group was higher in SBM than that in the FM group, while it was lower in FSM and SPC groups. In summary, compared to SBM, FSM, and SPC improved crayfish growth, maintained hepatopancreatic health, and stabilize intestinal microbiota composition to a certain extent.