Abstract In this study, we investigated the dietary effects of dandelion root extract (DRE) on growth performance, body composition, serum biochemical parameters, intestinal and liver histology, and fish resistance against Lactococcus garvieae infection in the rainbow trout. In total, 540 rainbow trout fry (22.05±1.740 g and 13.03±0.470 cm) were used. Six experimental groups (control, 2.5 mL/kg (DRE-1), 5 mL/kg (DRE-2), 10 mL/kg (DRE-3), 20 mL/kg (DRE-4), and 40 mL/kg (DRE-5) dandelion root extract) with three replicates were formed. In each tank, 30 fish were placed and fed for 90 days, and the volume of water was adjusted to 80 L with a flow-through system. The results showed that the final fish weight, weight gain, specific growth rate, protein efficiency ratio, and protein deposition rate were significantly higher in the DRE-4 group, while the feed conversion ratio and fat deposition ratio were significantly lower compared to that in the control group (P<0.05). The viscerosomatic index and the hepatosomatic index decreased in the experimental groups depending on the concentration of the extract used, while the condition factor was higher than that in the control (P<0.05). The DRE significantly decreased glucose, cholesterol, triglyceride, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase levels in blood serum in the fish from the experimental groups, but it significantly increased high-density lipoprotein, alkaline phosphatase, and total protein levels (P<0.05). Similarly, the DRE positively affected intestinal histology by increasing the stratum compactum, submucosa, lamina propria, villi length, villi width, absorption area, tunica muscularis thickness, mucosal folds, and goblet cell count. In the liver, depending on the high-fat diet (crude lipid = 20%), vacuolization areas, hepatocellular degeneration areas, apoptotic hepatocyte nucleus, and necrotic areas recorded in the control group decreased or even disappeared completely in the extract groups. The results of the challenge test showed that adding 2.5 mL/kg of the DRE to the feed positively affected the disease resistance against Lactococcus garvieae infection. The results of the quadratic polynomial regression showed that an average level of 23.91±1.048 mL/kg of DRE would be suitable for optimum fish growth.