This experiment investigated the effects of high carbohydrate diets supplemented with arginine on growth performance, body composition, plasma biochemistry, antioxidant activity, glucose metabolism and immune-related genes in juvenile hybrid snakehead [Channa maculata (♀)×C. argus (♂)]. The 450 hybrid snakehead with initial body weight of (22.02±0.02) g were randomly divided into three groups with three replicates of 50 fishes each and fed three experimental diets with carbohydrate levels of 21.34%, 27.45% and 27.38%, respectively, and were recorded as LC, HC and Arg groups for eight weeks. The results showed that compared with low-carbohydrate diet (LC group), high-carbohydrate diet (HC group) significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and protein deposition rate (PDR), and increased the feed ratio (FCR). The addition of arginine group (Arg group) significantly decreased FCR. Significantly improved the WGR, SGR, PDR, whole fish plasma protein and crude protein content. Compared with the LC group, the plasma and liver malondialdehyde (MDA) content and liver tumor necrosis factor-α (TNF-α) expression were significantly increased in the HC group. Intestinal total antioxidant capacity (T-AOC) and peroxidase (POD) and glutathione peroxidase (GSH-Px) and liver POD and GSH-Px activity, hepatic phosphoenolpyruvate carboxylase (PEPCK), glucose transporter protein-2 (GLUT-2), transforming growth factor (TGF-β) and heat shock protein 70 (HSP70) gene expression quantity dropped significantly. Oxidative stress and liver inflammation suggested liver disease in hybrid snakehead fed a high carbohydrate diet. Feeding the diet supplemented with Arg could enhance the antioxidant capacity of the liver by reducing the content of MDA and strengthening the activities of T-AOC, POD, GSH-Px and superoxide dismutase (SOD). Compared with the HC group, the expressions of pro-inflammatory factors interleukin-8 (IL-8), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were significantly decreased, and the expressions of anti-inflammatory factors TGF-β, HSP70 and heat shock protein 90 (HSP90) were significantly increased in C. maculata (♀)×C. argus (♂) fed with Arg diet. These results suggest the liver inflammatory response was relieved after dietary supplementation with Arg. Studies have shown that, Arg promoted insulin production and glycogenolysis by up-regulating the expression of insulin-related genes protein kinase B (AKT), insulin receptor subset-1 (IRS-1) and phosphatidylinositol-3 kinase (PI3K) and glucose metabolism-related genes PEPCK, glucose-6 phosphatase (G6P) and pyruvate kinase (PK) in the liver. Thus, it regulates hepatic glucose metabolism in fish. In conclusion, a high carbohydrate (HC group) diet induced oxidative stress and inflammation in C. maculata (♀)×C. argus (♂), while Arg supplementation enhanced antioxidant activity, alleviated inflammation, and promoted glucose metabolism.