Fish are extremely sensitive to many water-borne toxicants, due to theirprolonged, constant and direct contact with the aquatic environment where chemical exposure occurs over the entire body surface and ecological significance in any natural systems. This study investigated the effects of sodium fluoride on O. niloticus tissues and protection effect of Moringa oleifera to these tissues by exposed of O. niloticus to 1/10 dose of sodium fluoride 96hr-LC50 (6.1 mg/L) and study the changes in serum biomarkers of liver and kidney functions, total antioxidant capacity (TAC) and lipid peroxidation (LPO). Two hundred and sixty O. niloticus were used for determination of LC50 and chronic toxicity the fish divided into four groups of fifty fishes each. Control group, received no any treatment; 1/10 dose of sodium fluoride LC50 (6.1 mg/L), sodium fluoride plus Moringa oleifera powder and Moringa oleifera 1% of diet. The results showed that, sodium fluoride at dose of 6.1 mg/L significantly decreased serum total protein, albumin, globulin and TAC of O. niloticus. The ALT and AST activities and LPO contents of sodium fluoride exposed group was found higher than the M. oleifera supplemented groups.  On the basis of present findings it could be concluded that increased sodium fluoride content in water causes adverse effect on fish blood biochemistry. The changes of plasma biomarkers were the physiological responses of O. niloticus to the stress of sodium fluoride exposure. Moringa oleifera can be grown to produce more natural products and materials against heavy metals toxicity in aquatic ecosystem.