The present study was conducted to investigate the role of using the plant-based wastes as a supplementary diet in improving the hemato-biochemical blood status of Oreochromis niloticus and resistance against mercuric chloride toxicity (0.08 mg/l). Fish were distributed (10 fish/40-liter aquarium) into 8 groups. Control group and MC_0.08 group were fed on a commercial diet; MC/OFI_5% & MC/OFI_10% fed on a commercial diet supplemented with 5% and 10% Opuntia ficus-indica; MC/MO_5% & MC/MO_10% fed on a diet supplemented with 5% and 10% Moringa Oleifera; and MC/TO_5% & MC/TO_10% fed on diet supplemented with 5% and 10% Telfairia occidentalis. The experiment extended for 60 days in triplicates. The obtained results showed a significant increase (P<0.05) in WBCs, MCH, MCHC, glucose, cholesterol, uric acid, triglyceride, creatinine, and total bilirubin in MC_{0.08 group compared} to the control group. And a significant decrease in RBCs, HGB, MCV, HCT, protein, albumin, and globulin was noticed. Alteration in levels of GOT and GPT was also observed due to the toxic metal exposure. All diet supplementations improved the tested blood parameters (RBCs, HGB, MCV, HCT, protein, albumin, and globulin) compared to MC_0.08 group. A reduction was noticed in WBCs, MCH, MCHC, glucose, cholesterol, uric acid, triglyceride, total bilirubin, creatinine, GOT, and GPT. The degree of improvement among the three tested supplementations was arranged as Moringa Oleifera followed by Opuntia ficus-indica and Telfairia occidentalis. It was found that TO_10% can be efficient in enhancing fish health and blood characteristics. The dose 10% of MO and OFI were not effective and had no additional benefit. Our findings showed that the use of plant-based wastes as food supplements can improve blood properties and increase the ability of fish to resist the effects of toxins. The use of these materials is particularly promising because they are inexpensive and easily available.