Background: Trypanosomes cause the parasitic condition, which is transmitted by tsetse fly. The disease is characterized by intermittent fever, anemia, and frequent diarrhea. This study examined antioxidant and anti-trypanosomal effects of the aqueous extract of garlic in mice. Methods: The extract’s phytochemical screening and antioxidant activity were performed based on standard methods. The acute toxicity was evaluated via Lorke’s method and the anti-trypanosomal effect was evaluated in mice at 100, 250 and 500 mg/kg over 16 days. Results: The screening identified phenols, flavonoids, tannins, alkaloids and saponins. Phenols were present at the highest amount (291.88±6.12 mg/100g) and alkaloids were present the least (13.66±0.03 mg/100g). At 100 µg/mL, the extract quenched 53.20% of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals with an inhibition concentration (IC50) of 12.44 µg/mL. The lethal dose (LD50) of the extract was determined to be >5000 mg/kg in mice. The extract exhibited high anti-trypanosomal activity at 500 mg/kg and lowered the parasitemia count of 9.7±1.15. This was comparable to the diminazene aceturate activity at 5 mg/kg. The extract at 500 mg/kg significantly increased the packed cell volume and bodyweight of the infected mice. There were no significant differences in many hematological indices comparing the control mice to those that received the extract at 500 mg/kg. Conclusion: The garlic extract had a significant anti-trypanosomes effect and ameliorated the anemic condition induced by infection with trypanosomes. Therefore, the extract may become a therapeutic candidate for the management of trypanosomal infections.