The present study investigated the effect of fish meal (FM) replacement with fermented soybean meal (FSM) on growth performance, nutrient utilization, serum biochemical indices, intestinal histology, and microbial community of hybrid snakehead. Five isonitrogenous diets were formulated with FSM inclusion to decrease dietary FM from 350 g/kg (the control diet) to 300, 250, 200, and 150 g/kg, referring to CON, FM-30, FM-25, FM-20, and FM-15, respectively, and then fed to hybrid snakehead with initial body weight of for 60 days. The control group showed the best growth with a weight gain rate (WGR) of 417.0% and a feed conversion ratio (FCR) of 0.84, but the WGR in FM-25, FM-20, and FM-15 groups was decreased by 26.25%, 40.60%, and 42.23% and FCR was increased by 0.24, 0.45, and 0.45, respectively, when compared to those in the CON group ( ). The apparent digestibility coefficients of dry matter and crude protein, the protein efficiency and retention, the serum total cholesterol content, and the intestinal muscle thickness in FM-20 and FM-15 groups and the villus height in all FSM groups were significantly lower than those in the CON group ( ). Intestinal microbiota analysis indicated that the main microorganisms included Proteobacteria, Firmicutes, and Actinobacteria. At the genus level, Plesiomonas was the dominant genus with the highest relative abundance in the FM-20 group. In summary, in a diet containing 350 g/kg FM, FSM can successfully replace 50 g/kg dietary FM without negative effects on growth performance, nutrient utilization, serum biochemical indices, and intestinal health of hybrid snakehead juvenile.