Paris polyphylla Smith (family: Melanthiaceae), a high-value medicinal herb endemic to the Himalayan region, has drawn much attention recently due to its immense use in the traditional healthcare system since ancient times. In the present review, an extensive database on P. polyphylla was systematically searched from databases such as Medline/PubMed, Scopus, the Web of Science, and the online service E-library.ru and SCImago (https://www.scimagojr.com/). Information on species, ecology, distribution, trade, ethnopharmacology, pharmacology, biotechnology, and molecular biology was gathered from 1979 to 2023 using 116 research publications. Major steroidal saponins such as Paris saponin I, V, VI, VII, and H have been found substantially effective in anticancer activity, abnormal uterine bleeding, dysfunctional uterine bleeding, and menorrhagia. Traditional breeding and propagation techniques cannot keep up with the world’s growing demand for herbal drugs. Therefore, it is critically necessary to take conservation measures and develop novel techniques for growing and cultivating this economically significant and highly valuable therapeutic herb. The advanced biotechnological approaches like micropropagation and genetic analysis introduced long back are either rare or lacking in the case of P. polyphylla. It contains a wealth of information that will serve as a baseline data source for various stakeholders, researchers working on various research aspects, and policymakers to define appropriate utilization and conservation plans for a high-value commercial medicinal plant called P. polyphylla. The review provides an updated overview and critical assessment of secondary data regarding the past and recent applications and interventions of P. polyphylla.