Silver catfish (Rhamdia quelen) is an important fish in aquaculture in southern Brazil. Despite good aquaculture practices, this fish has a high mortality rate caused by recurrent infection by bacterial pathogens. In response to the worldwide battle against the reckless use of antibiotics, we proposed the use of a naturally derived antibacterial component—the essential oil of lemongrass; Cymbopogon flexuosus (EOCF). This study aimed to assess its impact on intestinal morphology, oxidative status, and mortality control in fish exposed to Aeromonas hydrophila. The EOCF was included in the diet (0.0-control, 0.25, 0.5, 1.0 g/kg of feed) of silver catfish juveniles (mean individual weight of 12 g) stocked in aquariums of 70 L (17 fish by tank), in a trial for 25 days in a recirculating aquaculture system. In the initial experimental stage, natural infection by A. hydrophila led to the complete loss of animals in the control group. Therefore, a new control group without EOCF in the diet or infection was implemented, which allowed morphometric and biochemical comparison with the infected groups. At the end of the experiment, 8 fish per treatment were anesthetized and euthanized with a spinal cord section to collect biological material. Muscle and liver were removed, frozen, and stored at -80°C for further analysis. The gastrointestinal tract (GIT) was removed and placed in 10% neutral formalin for histological tests. The measurement of the oxidative stress biomarkers was determined by the lipid peroxidation levels by the test of thiobarbituric acid reactive substances (TBARS) and superoxide anion. And the enzymatic antioxidant defense system was evaluated from the enzymatic activity of Total Superoxide dismutase (SOD), Glutathione S-transferase (GST) and Catalase (CAT), additionally the Total Antioxidant Capacity (TAC) was determined. The intestine samples were subjected to Goldner’s Trichrome staining and then photographed at 2.5x magnification and measured in the ImageJ program. The results concerning this study were expressed as means ± standard deviation (SD) and were analyzed by one-way analysis of variance (ANOVA) using R software (version 4.1.0). A significant difference was expressed at the p < 0.05 level. The EOCF nanoemulsion significantly increased SOD (0.25 g/kg of EOCF per diet), GST (0.25 and 0.5 g/kg of EOCF per diet), and CAT (0.5 and 1.0 g/kg of EOCF per diet) activity in muscle, but did not significantly change TBARS levels in the liver. The histomorphology showed that the number of goblet cells and height of the villi was reduced in animals that received a dose of EOCF nanoemulsion higher than 0.5 g/kg of EOCF per diet. Finally, supplementation with 0.25 g/kg of feed significantly reduced mortality. In conclusion, EOCF is a promising nutraceutical ingredient, that can improve the oxidative status and histomorphology of the GIT in the feed formulations of juvenile silver catfish while enhancing disease resistance against A. hydrophila.