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The objective of the present study was to investigate the effects of different doses of dietary Eucommia ulmoides leaf extract (ELE) on juvenile red claw crayfish (Cherax quadricarinatus). A total number of 720 red claw crayfish (initial body weight of 0.24 ± 0.01 g) were randomly assigned to six groups and fed diets containing 0 (Diet 1), 0.5 (Diet 2), 1 (Diet 3), 2 (Diet 4), 4 (Diet 5) and 10 (Diet 6) g dry weight (dw) ELE kg (dw)−1 diets for eight weeks and challenged with microcystin-LR stress. The results indicated that dietary supplementation with 1–2 g dw ELE kg (dw)−1 diet could significantly improve the weight gain rate (WGR) and specific growth rate (SGR) of crayfish. Muscle crude protein contents of crayfish fed Diet 2, Diet 3, and Diet 4 were significantly higher than those of the control group. Compared with the control group, dietary ELE could increase total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GPx), acid phosphatase (ACP), alkaline phosphatase (AKP), and phenoloxidase (PO) activities and decrease malondialdehyde (MDA) level of crayfish. Dietary ELE significantly increased the relative expression levels of SOD, thioredoxin 1 (TRX1), GPx, selenium-dependent glutathione peroxidase (Se-GPx), cytochrome P450 (CYP450), anti-lipopolysaccharide factor (ALF) and C-type lysozyme (C-LZM) mRNA of crayfish compared with the control group during the feeding experiment. When subjected to MC-LR stress for 48 h, the mRNA expression levels of SOD, GPx, Se-GPx, glutathione-s-transferase 1 (GST1), ALF, hemocyanin (HEM), and C-LZM in the hepatopancreas could be improved to varying degrees compared with the Diet 1. Supplementation of 1–2 g dw ELE kg (dw)−1 diet could improve the survival rate (SR) of crayfish under MC-LR stress. These results indicated that dietary ELE (1–2 g dw ELE kg (dw)−1 diet) could improve the growth performance, muscle protein, and non-specific immune response and increase the SR of crayfish under MC-LR stress by regulating the mRNA expression levels of the immune- and antioxidant-related genes.