This study investigated the effect of prolonged consumption of ethanolic seed extract of Monodora myristica (ESEM)for 21 day on some liver function enzymes and antioxidant status in rats. Eighteen (18) male Wistar rats were randomly divided into three groups (n=6) and treated orally as follows: Group I: (Control) received 0.4 mL of 0.1 % vehicle (tween 80) for 21 consecutive days; Group II: (Low dose) and Group III (High dose) received 50 mg/kg and 100 mg/kg of ethanolic seed extract of Monodora myristica (ESEM) for 21 consecutive days respectively. The animals were sacrificed under anaesthesia (via ketamine; 90 mg/kg) 24 h after the last treatment. Blood and liver tissue samples were collected and processed for analysis of some liver function parameters and antioxidant status. The oral LD50 value of ESEM in rats exceeded 5000 mg/kg body weight, indicating a relatively low toxicity. ESEM administration for 21 days at doses of 50 mg/kg and 100 mg/kg significantly (p<0.05) improved the serum levels of ALT (13.60±0.40 U/L; 12.42±0.42 U/L), AST (24.24±0.88 U/L; 21.19±0.90 U/L) and GGT (1.86±0.07 U/L; 1.15±0.08 U/L) compared to the normal control group (16.40±0.46 U/L; 28.46±0.94 U/L; 2.44±0.10 U/L) respectively. Normal level of SOD (9.24±0.12 U/mg protein) and CAT (1.74±0.04 µmol/min/mg protein) were significantly increased to 10.44±0.10 U/mg protein; 2.03±0.02 µmol/min/mg protein and 11.98±0.14 U/mg protein; 2.42±0.05 µmol/min/mg protein, in the animals that received 50 and 100 mg/kg of ESEM respectively. Also, the normal concentration of MDA (1.05±0.03 nmol/mg protein) was significantly (p<0.05) attenuated to 0.82±0.04 and 0.65±0.02 nmol/mg protein, in the animals that received oral administration of ESEM at 50 mg/kg and 100 mg/kg respectively. The findings suggest that long-term use of ethanolic seed extract of Monodora myristica at low dose is unlikely to induce hepatotoxicity, but rather exerts hepatoprotective effects, enhancing the overall liver health. Keywords: Prolong consumption, Monodora myristica seed, oral administration, hepatoprotective, liver enzymes, antioxidant system