Humans and animals are constantly exposed to crude petroleum contaminated diets in petroleum producing areas of the world. As a result, researches are on-going to find simple ameliorative agent against crude petroleum contaminated diet toxicity. The aim of this study was to evaluate the protective effect of Monodora myristica on some biochemical parameters of rats fed with crude petroleum oil contaminated catfish diet (CPO-CCD). Thirty male albino rats were separated into six groups of five rats as follows: group 1: control, group 2: rats were fed CPO-CCD only, group 3: CPO-CCD plus 1 ml/kg of 1 % tween 80, group 4: CPO-CCD plus M. myristica water extract (MWE), group 5: CPO-CCD plus M. myristica ethanol extract (MEE) and group 6: CPO-CCD plus M. myristica diethyl ether extract (MDEE). The feeding of the rats with CPO-CCD and administration of extracts orally lasted for 28 days. The results showed significant (P < 0.05) increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in the serum and tissues (liver, kidney and brain) and decrease in total protein, albumin and globulin in the serum and liver of group 2 and 3 when compared with group 1. Significant (P < 0.05) decrease in AST, ALT, ALP activities and increase in total protein, albumin and globulin levels were observed after treatment with M. myristica extracts (group 4, 5, and 6) when compared with group 1. However, it could be concluded that MDEE revealed a strong effect when compared with the MEE and MWE.