Background: Areca nut, the nut of the areca palm (Areca catechu L.) and the leaf of betel vine (Piper betle L.) are the two inevitable ingredients of the common chewing mixture popularly known as betel quid. Both traditional and modern research findings proved that these two plant products have many medicinal values, including anticancer properties. With this information, we formulated a polyherbal preparation chiefly containing these two plant products and evaluated its anticancer efficacy on the specific cancer cell line. Methods: The polyherbal preparation called ‘Pugasaram’ was prepared using 12 different plant products, including areca nut and betel leaf, in different proportions. It was screened for its anticancer properties against A549 cancer cell lines. Results: The study showed a dose-dependent cytotoxicity of ‘Pugasaram’ on cultured A549 cancer cells with the IC50 value of 109.32 µg/ml. Conclusion: The present study reveals great potential for ‘Pugasaram’ to develop as an effective anticancer drug. This information could be the basis for further studies in this field.