Abstract: This study investigated the effects of replacing soybean meal and rapeseed meal with fermented distiller’s grains (FDG) on the growth performance, immunity, and antioxidant capacity of grass carp (Ctenopharyngodon idella). Five experimental diets were formulated: a basal diet (control group, CON), and diets in which FDG replaced 2.5% soybean meal (ZD1), 5% soybean meal (ZD2), 3% rapeseed meal (ZC1), or 6% rapeseed meal (ZC2). Each treatment comprised three replicates of 50 fish per cage, and grass carp with an initial average body weight of 24 g were fed for 56 days, with parameters assessed including growth performance, serum biochemical and immune indices, intestinal digestive enzyme activities, histomorphology, and the expression of antioxidant- and inflammation-related genes in the liver and intestine. Results showed that compared with the control group, the ZD2 and ZC1 groups exhibited significantly higher final body weight, weight gain rate, and specific growth rate, as well as a significantly lower feed conversion ratio (P<0.05). These groups also showed significantly decreased serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels, while the levels of high-density lipoprotein cholesterol (HDL-C), complement 3 (C3), complement 4 (C4), immunoglobulin M (IgM), and acid phosphatase (ACP) were significantly increased (P<0.05). Similarly, the ZD2 and ZC1 groups also exhibited significantly higher activities of amylase, lipase, and trypsin (P<0.05). Histomorphological results showed significantly increased intestinal goblet cell count, villus height, and muscularis thickness, as well as clear hepatic boundaries, distinct nuclei, and normal hepatocyte morphology. In terms of hepatic and intestinal antioxidant capacity, the ZD2 and ZC1 groups significantly increased the activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), while decreasing malondialdehyde (MDA) content, and significantly upregulated mRNA expression of antioxidant-related genes (gpx1a, gpx4a, CuZnsod, cat) in the liver and intestine. Furthermore, compared with the control group, the ZD2 and ZC1 groups significantly increased the mRNA expression of anti-inflammatory factors (il-10, tgf-β1) and decreased the mRNA expression of pro-inflammatory factors (nf-κb, tgf-α, tlr4) in the liver and intestine; in addition, the mRNA expression of intestinal tight junction-related genes (zo-1, occludin, claudin-c) was significantly upregulated. In conclusion, these findings indicate that FDG can effectively replace 5% soybean meal and 3% rapeseed meal in grass carp feed, thereby promoting growth performance and enhancing antioxidant capacity and immune function in the liver and intestine, with the 5% soybean meal substitution exhibiting the most prominent effects.