Toxicological evaluation of 25 and 50 mg/kg body weight of acetone thiosemicarbazone (ACTSC) and its metal complexes were investigated. A total of forty-five (45) male wistar rats used were randomly divided into nine (9) groups (labelled A - I) of five (5) rats each per group i.e. Group A=(Control 5% DMSO); B=(ACTSC 25 mg/kg); C= (ACTSC 50 mg/kg); D=(ACTSC-Cu2+ 25 mg/kg); E=(ACTSC-Cu2+ 50 mg/kg); F=(ACTSC-Zn2+ 25 mg/kg); G=(ACTSC-Zn2+ 50 mg/kg); H=(ACTSC-Ni2+ 25 mg/kg) and I=(ACTSC-Ni2+ 50 mg/kg). After five days of oral test drug administration, the animals were anaesthetized and blood samples collected via cardiac puncture into sample bottles for biochemical analysis (bilirubin total and conjugated, total protein, albumin, globulin. Albumin/globulin ratio), antioxidant status (superoxide dismutase, catalase, and malondialdehyde) and liver enzyme activity (AST, ALP and ALT).Tissues (liver) were also excised for histopathological examination. Analysis of test results obtained indicated both doses of the ACTSC and 50mg/kg body weight of ACTSC–Cu2+ caused significant increase (P< 0.05) on liver weight and liver/body weight ratio, in the same vein both doses of the ACTSC also caused significant effects (P< 0.05) on total and conjugated bilirubin, albumin, globulin and albumin/globulin ratios while only the 50 mg/kg body weight of ACTSC–Zn2+ had significant effect (P< 0.05) on globulin and albumin/globulin ratio. Antioxidant evaluation of the test samples indicated that both doses of ACTSC and ACTSC-Zn2+ complexes caused significant increase (P< 0.05) in MDA, however both doses of the ACTSC and 50 mg/kg body weight of ACTSC–Zn2+ caused significant decrease (P< 0.05) in catalase and superoxide dismutase activity. Investigation of the test samples on liver enzymes showed that both doses of ACTSC and ACTSC-Zn2+ caused significant increase in AST and ALP and ALP. Histopathological examination of the liver showed that the groups treated with 25 mg/kg body weight of the complex of ACTSC-Zn2+, 25 and 50 mg/kg body weight of the complexes of ACSTC-Cu2+ and ACTSC-Ni2+ showed strong similarity with the control group by having well preserved lobular architectures, normal hepatocytes, normal central vein, capsules with no indication of adhesion and inflammation.