Purpose: The use of medicinal plants in malarial treatment has become popular in Nigeria, an endemic country, due to failing chemotherapy and high cost of antimalarial drugs. One of such commonly used herbs is Phyllanthus amarus. The antimalarial activity of P. amarus has been consistently reported, giving credence to its traditional use. Nevertheless, effects of such treatment on reducing cardiovascular risk indices is yet to be fully documented. This is imperative since certain metabolic complications like increased plasma lipids have been associated with considerable risks of fatty liver and cardiovascular diseaes in severe cases of malaria in humans. Methods: In this present study, therefore, the antiplasmodial action of the ethanol root extract of P. amarus and its ED50 dose were determined and associated cardiovascular risk indices were evaluated in BALB/c malarial infected mice, having ascertained the nutritive quality and phytochemicals of plant root. Results: Results showed that P. amarus root is abundant in alkaloid phytochemical and the roots extracts demonstrated significant antiplasmodial activity in a dose-dependent trend with optimal ED50 and maximal potency in reducing cardiovascular risk indices (Atherogenic index of plasma, AIP and heart disease risk, HDR) and fatty liver, which compared well with the values obtained from the uninfected control mice. Conclusion: The roots of P. amarus possess a wide array of nutrients and phytochemicals, with significant antimalarial activity. The roots also reduced the risks of cardiovascular diseases associated with severe malaria, in experimental mice.