The present work aimed to detect the toxicological impacts of oxyfluorfen (herbicide) on hematological and biochemical parameters of Oreochromis niloticus and the prophylactic role of garlic acid and curcumin in detoxification. Adult fish were exposed to two sublethal concentrations (0.3 and 0.6ppm) of oxyfluorfen against 5g/ kg of curcumin and 5g/ kg of garlic acid for detoxification role for 2 and 4 weeks. Erythrocyte count (RBCs), hemoglobin content (Hb), hematocrit value (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and leucocytes count (WBCs) as hematological markers were measured. Biochemical parameters included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) enzyme activities, serum protein (total protein, albumin and globulin) concentration, urea, creatinine, sodium (Na), potassium (K), glucose, cholesterol (Cho) and triglyceride (Tg). The present investigation showed that oxyfluorfen in different doses led to a significant reduction (P< 0.05) in RBCs, Hb, Hct, MCV, MCHC, PLT, WBCS, neutrophils (Neut), monocytes (Mono), serum Cho and Tg. However, compared to the control group, MCHC, lymphocytes (Lymp), AST, ALT, ALP enzyme activities, serum proteins (total protein, albumin and globulin), urea, creatinine, glucose, Na and K showed a significant increase (P< 0.05). Garlic acid and curcumin played an optimistic role in the detoxification of oxyfluorfen toxicity. The findings implied that oxyfluorfen had a deleterious impact on fish hematological and biochemical markers. In addition, curcumin and garlic demonstrated an improvement in hematological and biochemical markers regarding the removal of oxyfluorfen toxicity.