Lack of available vaccines and emerging resistance on the anti-malarial drug have provided the necessity to find noble plant--based anti-malarial drugs. The leaf latex Aloe weloensis has been used in folk medicine against malarial and other human ailments in Ethiopia. Hence, the present study aimed to investigate the anti-malarial activity of the leaf latex of A. weloensis against Plasmodium parasites to validate its traditional claim. Methods: The leaf latex of A. weloensis was evaluated in vitro anti-malarial activity against 3D7 strain of Plasmodium falciparum. The prophylactic and curative models were employed to determine in vivo anti-malarial activity of the latex against P. berghei infected mice, and antioxidant activity of the leaf latex of A. weloensis was assessed in DPPH assay. Results: The leaf latex of Aloe weloensis endowed with free radical inhibition activity (IC50 = 10.25 μg/ml). The latex of A. weloensis leaf was demonstrated inhibitory activity against 3D7 strain of P. falciparum (IC50 = 9.14 μg/ml). The prophylactic and curative effect of the latex was found to be dose-dependent. Parasitemia reduction was significant (200 mg/kg, p<0.01, 400 and ,600 mg/kg, p<0.001) in prophylactic test compared to the control. Parasitemia level of the mice treated with 200, 400, and 600 mg/kg doses of the latex significantly (p<0.001) reduced with suppression of 36%, 58%, and 74% respectively in the curative test. The leaf latex significantly (p<0.01) improved mean survival times, packed cell volume , rectal temperature, and bodyweight of P. berghei infected mice. Conclusion: The result was confirmed the anti-malarial activity of the leaf latex of Aloe weloensis at various doses which corroborates the traditional uses of the plant.