The substitution of fishmeal with plant proteins can induce oxidative stress in aquatic animals and impair their growth and health. Quercetin is a potent natural antioxidant, but its specific effects on the growth and health of Chinese mitten crabs, as well as the underlying molecular mechanisms, remain unclear. This study aimed to investigate the impact of quercetin on the growth, physiological and biochemical parameters, gut microbiota, and transcriptome of juvenile Chinese mitten crabs (Eriocheir sinensis). Crabs (0.53 ± 0.01 g) were randomly divided into seven groups. One group was fed a diet containing normal fishmeal (35 % fishmeal), whereas the other six groups were fed diets containing low levels of fishmeal (15 % fishmeal) supplemented with different levels of quercetin (0, 250, 500, 1000, 2000, or 4000 mg/kg). Each group had four replicate tanks with 40 crabs per 300 L tank, and the experiment lasted for 56 days. The growth performance of the 35 % fishmeal group was significantly greater than that of the 15 % fishmeal group without quercetin. However, quercetin significantly increased the weight gain rate and specific growth rate of juvenile crabs, especially in the 1000 mg/kg quercetin group, where these rates exceeded those of the normal fishmeal group. The antioxidant capacity and immunity of the 35 % fishmeal group were significantly greater than those of the 15 % fishmeal group. However, quercetin supplementation promoted the antioxidant capacity and immunity of the crabs. Quercetin supplementation at 4000 mg/kg changed the gut microbiota structure by decreasing beneficial bacteria and increasing pathogenic bacteria. Quercetin supplementation enhanced the growth performance and antioxidant capacity of Chinese mitten crabs by increasing glutamate metabolism, pantothenic acid and Coenzyme A biosynthesis, sphingolipid metabolism, arachidonic acid metabolism, and cysteine and methionine metabolism. This study revealedthat dietary supplementation with quercetin can promote Chinese mitten crab growth, antioxidant capacity, and nonspecific immunity; improve gut morphology; and promote gut microbiota homeostasis. The optimal dietary concentration of 688–695 mg/kg is recommended on the basis of weight gain and specific growth rate analyses.