This study was conducted to evaluate the toxicity and activity of Rubia cordifolia, Harrizonia abyssinica, Leucas Calistochys Olive and Sanchus schwein furthii against Plasmodium berghei. Approximately 1x105-1x106 of parasitized erythrocytes with Plasmodium berghei, were inoculated into 7 week old naïve BALB/c mice. On the fourth day, these mice were treated with four plant extracts dispensed using the following dosage; 25mg/kg of body weight, 50mg/kg of body weight, and 100mg/kg of body weight twice daily for 4 days. The negative control group received equal dosage of normal saline. Results showed that Rubia cordifolia and Sanchus schwein furthii had higher anti-plasmodial activity against P. berghei parasites with values of 82.4 % (p = 0.001) and 78.6% (p = 0.003). All the mice treated with the above extracts survived up to day 15 just as the controls. The percentage parasitaemia reduction in mice treated with extracts of Harrizonia abyssinica and Leucas Calistochys also showed values of 65.1% (p=0.011) and 59.1% (p=0.04) respectively. LD50 doses of <10mg/kg were observed. Harrizonia abyssinica and Leucas Calistochys Olive had moderate parasite suppressive effects with LD50 doses ranging between 10mg/kg and 100mg/kg. The aqueous extracts of Rubia cordifolia, and Sanchus schwein furthii were more efficacious with highest parasitaemia suppression on Plasmodium berghei