An 8-week trial was performed to investigate the effects of replacing soybean meal (SBM) by sunflower meal (SM) or enzymolysis sunflower meal (ESM) on the growth, lipid metabolism, and intestinal health of Ctenopharyngodon idellus. Compared with SM, the small peptides and amino acids contents in ESM increased, while the crude fiber decreased. Seven isonitrogenous and isolipid diets (SM0, SM25, SM50, SM75, SM100, ESM75, and ESM100) were prepared for SM to replace 0, 25, 50, 75, 100% SBM and ESM to replace 75 and 100% SBM, respectively. The results showed that with an increasing proportion of SM instead of SBM, weight gain rate (WGR) of grass carp showed a decreasing trend, while feed conversion ratio (FCR) showed a rising trend, and significantly changed in the SM75 and SM100 groups. WGR in the ESM75 group was significantly increased compared with the SM75 group, and there was no statistical difference with the SM0 group. Replacing 75% and 100% SBM with ESM was beneficial to lipid metabolism, which was mainly manifested in decreased serum low-density lipoprotein, triglyceride, and total cholesterol contents, and significantly down-regulated acetyl-CoA carboxylase (acc), fatty acid synthase (fas) and sterol regulatory element binding protein 1 (srebp1) gene expression in liver. Replacing 75% and 100% SBM with SM resulted in intestinal oxidative damage (reactive oxygen species and malondialdehyde contents increased; superoxide dismutase, glutathione reductase, and glutathione peroxidase activities decreased) and disrupted intestinal physical and immune barrier functions (claudin15, myosin light chain kinase (mlck), interleukin-1β, 6, 12β (il-1β, il-6, il-12β), tumor necrosis factor-α (tnf-α), and nuclear factor-κB (nf-κb) gene expression up-regulated; zonula occluden 1, 2 (zo1, zo2), transforming growth factor β1 (tgf-β1), and il-10 gene expression down-regulated), while substitution of 75% and 100% SBM by ESM alleviated oxidative damage and improved intestinal immune and physical barrier functions. In addition, the α-diversity index and the abundances of Erysipelatoclostridium and Bacteroides in the ESM75 group were significantly increased compared with the SM0 and SM75 groups. In conclusion, the replacement proportion of SBM with SM should not exceed 50%, otherwise it will lead to reduced growth, lipid deposition, intestinal health damage and intestinal microbiota disorder. However, the replacement of 75% SBM with ESM has no negative effect on grass carp, and it improved lipid metabolism and intestinal health compared with substitution of SBM with SM.