The prospective effect of beetroot extract (Beta vulgaris L.) to resist the toxic effect of lead (Pb) and enhance the immune status and antioxidant enzyme of the Nile tilapia (Oreochromis niloticus) was studied. Fish specimens were divided into 4 groups: C (control group), Pb (group subjected to lead), T1, and T2 (groups injected intraperitoneal with 100 and 150mg/ kg of beetroot extract 2 weeks before being subjected to Pb, respectively).  The effects were addressed on the humoral immune parameters, (antiproteases, lysozyme total protein, and globulin) and antioxidant enzymes [Glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) activities], as well as some biochemical parameters. Pb accumulation was studied in gills, liver, and muscle tissues. The results revealed a significant enhancement in some immune parameters viz. a lysozyme and total protein in T1 groups compared to other groups, especially with the Pb group which showed the lowest significant values (P< 0.05). The groups injected with beetroot extract showed the lowest significant values (P< 0.05) of Pb accumulation in tissues compared to Pb group. While, T1 group recorded a significant increase (P< 0.05) in hepatic protein content, GST, SOD, CAT, and POX, respectively, compared to the Pb group. Moreover, Pb group showed a significant decrease compared to the control group. Most of the biochemical parameters, including glucose, cholesterol, AST, and uric acid recorded the highest values in Pb group compared to the other groups, but without significant difference. The albumin value of T1 group showed the highest significant values compared to other groups. To conclude, the injection of the Nile tilapia with 100mg/ kg of beetroot extract may contribute to protecting fish from the harmful effects of lead by enhancing the immune system and antioxidant enzymes, and improving the general fish health.