Podophyllum hexandrum Royle, synonym P. emodi Wall, also known as Himalayan mayapple, is a high-altitude medicinal herb belonging to the family Berberidaceae. This species is a rich source of pharmacologically active compounds, most notably podophyllotoxin, a powerful lignan used as a precursor for anticancer drugs. In addition to podophyllotoxin, the plant contains other bioactive constituents such as flavonoids, lignans, and phenolic acids, contributing to its therapeutic potential. Due to unscientific overharvesting from its natural habitat in the Himalayan region and its inherently slow growth and regeneration rate, P. hexandrum is now considered a rare and endangered species. The increasing pharmaceutical demand, coupled with ecological pressures, underscores the urgent need for conservation. In situ and ex situ conservation strategies, along with cultivation protocols for mass propagation, are critical to prevent extinction and ensure a sustainable supply. Techniques such as micropropagation, rhizome division, and cultivation in agro-climatic conditions mimicking its native habitat have shown promise. This chapter explores the medicinal properties of Podophyllum hexandrum, along with its botanical characteristics, phytochemical composition, rarity, and conservation through biotechnological approaches.