A 90 days of feeding trial was employed for evaluating the effects of dietary supplementation with curcumin nanoparticles (CURNPs) on growth performance, hematological and biochemical parameters, immune response, antioxidant status, and intestinal and hepatic architecture in European seabass (Dicentrarchus labrax) fingerlings. Fish (n = 300, initial body weight = 10.02 g ± 0.11 g) received supplementary CURNPs at rates of 0 (control; CURNPs0), 50 (CURNPs50), 100 (CURNPs100) and 150 (CURNPs150) mg/kg diet for 90 days. Growth performance (final body weight (FBW), daily weight gain (DWG), weight gain (WG), relative growth rate (RGR), and protein efficiency ratio (PER)) and feed uptake (feed conversion rate (FCR)) were improved significantly in CURNPs (100 and 150 mg/ kg)-supplemented groups. The hematological parameters red blood corpuscles (RBCs), hemoglobin (Hb), and packed cell volume (PCV) were improved significantly (P<0.001) in CURNPs150 and CURNPs100 groups, while CURNPs150 had the lowest values of monocytes (P = 0.019) and heterophils (P<0.005) when compared with other groups. Glucose was higher and lipid profile (total cholesterol and triglycerides) were lower in all CURNPs-supplemented groups as compared to the control group. Fish fed with CURNPS at various levels exhibited remarkable increase in digestive enzymes (amylase and lipase), immune markers (immunoglobulin G (IgG), lysozyme and phagocytic indices), and antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)). A noticeable decrease (P<0.05) in malondialdehyde (MDA) and considerable upregulation of hepatic insulin-like growth factor 1 (IGF1) and interleukin-1beta (IL-1β) mRNA levels were found in CURNPs-supplemented fish in a dose-dependent manner. The down regulation of hepatic heat shock protein 70 (HSP70) was observed in CURNPs150. Intestinal and hepatic architectures were improved significantly by CURNPs. In conclusion, CURNPs supplementation improved growth performance, feed consumption and digestion, hematological and biochemical markers, immune response, and redox homeostasis in D. labrax. Therefore, CURNPs could be supplemented in the diets of D. labrax as a natural alternative to promote overall performance.