Malaria is a tropical disease that has constitutes a major health problem and big challenges for drug discovery because of the frequent chemoresistance to most available drugs in the market. In the present study, Nickel(II) Chloride Hexahydrate were used to complex the mixed Mefloquine and Pyrimethamine (an antimalarial drugs). The complex of the type ML1L2 were formed [Where M=Ni, L1=Mefloquine and L2=Pyrimethamine]. The compound was characterized by elemental analysis, conductivity, IR, UV-VIS and magnetic measurements. The chelate do not show toxicity against alkaline phosphatase (ALP) activities of enzymes from the homogenates of liver, kidney and serum of the experimental rats. Antimalarial activities of the complex were investigated using mice infected with Plasmodium berghei. The results show that the mixed metal complex exhibited significant higher antimalarial activity with the highest percentage inhibition of 70.3% at 25mg/kg dosage. Overall, the metal chelate possesses a better physical properties and enhanced biological activities due to complexation with metal as compared to their parent compounds.