Abstract:Introduction: The disulphide derivative of dihydroartemisinin was synthesized and confirmed of being effective against Plasmodium berghei berghei, some gramme positive bacteria and fungi. Objective: The study was designed to compare the effect of the synthesized disulphide derivative of dihydroartemisinin with pure dihydroartemisinin on biochemical, histological and hematological parameters. Method: Doses of 10%, 20% and 30% of the LD 50 of pure dihydroartemisinin and its disulphide derivatives were orally administered to each group of rat for 14 days. On the 14 th day, the rats were sacrificed, and blood collected by cardiac puncture was used for hematological and biochemical studies. The liver and kidney were removed, weighed and preserved in 10% formalin for histopathology studies. Results: Using Lork's method, the LD 50 for pure dihydroartemisinin was 547.72 mg/kg while the disulfide derivative was 346.41mg/kg. There was a significant difference (p<0.05) in the concentrations of hematological parameters in treated rats from those of the control group. There was a dose dependent increase in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the treated groups. The cells of the liver and kidney were slightly affected by all the doses of dihydroartemisinin and moderately by the disulphide derivative. Conclusion: The toxicity of dihydroartemisinin (DHA) and its disulphide derivative (SDHA) are almost the same, making the SDHA not too toxic for animals. The effect of SDHA on the liver, kidney and hematological parameters are more than those of DHA, however they are within tolerated range. Clinical and therapeutic effectiveness should determine the comparative advantages of the newly synthesized SDHA over DHA and vise versa.