Eighty healthy Wistar albino rats were used to investigate the trypanocidal effect of natural and synthetic supplements of zinc and magnesium in combination with diminazene aceturate in Trypanosoma congolense-inoculated rats. The rats were randomly divided into eight groups in study ‘1’ (involving the natural supplements of zinc and magnesium) and eight groups in study ‘2’ (the synthetic supplements ZnCl2 and MgCl2), each group of both studies having five rats. Hence, studies 1 and 2 had groupsA - H each. Parasitaemia of trypanosome parasite was assessed using ‘wet mount method’ after inoculation of all test groups except group ‘G’ of both studies (the normal, not infected, not treated control). Group ‘E’ of both studies in which combinations of natural source of zinc ion (maize bran) and magnesium ion (wheat bran) were combined with subtherapeutic dose of diminazene aceturate at 1.75 mg/kg cleared the trypanosome parasites with no relapse. The salts supplements of ZnCl2 and MgCl2 with the same subtherapeutic dose of diminazene aceturate also elicited an effect similar to the group ‘E’ in natural supplementation study. There was thus, no significant difference (p>0.05) between the PCV and RBC of normal group ‘G’ and the natural and synthetic supplemented groups with the trypanocide. The groups B, C, and D of both studies however, onlyprolonged the live of the animals (though with relapse occurring) there was still the death of the animals before the end of the experiment. The improvement of PCV and RBC values of treated groups ‘E’ in the two studies towards the normal gave credence to the fact that the supplements of Zn2+ and Mg2+ with the subtherapeutic dose of 1.75 mg/kg had a better trypanocidal and rejuvenating tendency and could be used for treatment.