Objective: To investigate in-vivo anti-plasmodial activity of aqueous extracts of plants selected based on the symptomology mentioned in Ayurveda. Methods: The aqueous extracts of Holarrhena antidysentrica (H. antidysentrica) (Kutaja) and Azadirachta indica (A. indica) (Neemb) for their antiplasmodial potential in Plasmodium berghei (P. berghei) infected mice was assessed using Peters four day suppressive test. Both the extracts were administered at 2 dose levels, full dose (1 000 mg/d) and minimized dose (200 mg/d). 106 P. berghei infected RBCs were injected on day ’0’ and treated from day ’0’ till day ’3’ post-infection. Tail blood smears were collected, giemsa stained and analyzed. The mice were observed for survival and parasitemia was assessed till 50% of mice in control survived. Results: It was observed that the percentage of parasitemia increased gradually in all the groups, with maximum in control group (Day 3-35, Day 9-46.98) and minimum in Chloroquine arm (Day 3-14.06, Day 9-19.92). The percentage of parasitemia was compared using Mann-Whitney U test depicting that all test groups exhibited reduction in parasitemia as compared to control (P-value<0.002 for all groups). These groups showed similar percentage of survival as Chloroquine. Conclusions: The present investigation demonstrated the anti-plasmodial effects of H. antidysentrica and A. indica, which are two most commonly used medicinal plants in Ayurved for treatment of fever.