BACKGROUND: The emergence and spread of Plasmodium falciparum resistance to antimalarial drugs necessitated the search for new drugs from natural products. Zingiber officinal Roscoe and EchinopsKebericho Mesfin are traditional herbal medicines widely used for the treatment of malaria in Ethiopia. The aim of the study was to assess the toxicity profile and in vivo antiplasmodial activities of 70% methanol crude extracts of both plant materials against Plasmodium berghei.METHODS: Healthy male Swiss Albino mice of age 4-5 weeks and weight 25-36 g were infected by P. berghei. The extracts were administered orally at doses 5000, 2500 and 1250 mg/kg for acute toxicity of E. kebericho Mesfin. Graded doses at 1000, 500 and 250 mg/kg used for four days suppressive studies. Parasitemia, body weight, packed cell volume (PCV) and survival time were determined.SPSS Version 20 was used for the analysis of data of parasitemia, body weight, PCV, and survival times.Statistical significance was determined by one-way ANOVA. Independent t-test was used to compare results. Resultswere presented as a mean ± standard error of the mean (M ± SEM). All data were analyzedat a 95% confidence interval (α= 0.05).RESULTS:At the dose of 5000 mg/kg,E. kebericho Mesfinshowed no toxic effects. The LD50 of extract could go beyond the dose used. In vivoantiplasmodial activity of extracts showed excellent chemo suppression at 500 and 1000 mg/kg in a dose dependent mannercompared with the negative control. The chemo suppressions of the 1000 mg/kg of both plant extractswere 49.53 ± 1.90% and 32.83 ± 1.03%,respectively. The survival times of P. berghei infected mice were also a dose dependent manner while failed to prevent weight loss.CONCLUSION: The extracts of both medicinal plants showed antiplasmodial activities against P. berghei. It confirmed the literature findings and their traditional uses.KEYWORDS:Echnops kebericho Mesfin, Zengibir officinale Roscoe, Plasmodium berghei, oral acute toxicity, antiplasmodial