Ethnopharmacological relevanceThe people of the Pan-Himalayan region are among the most isolated and economically disadvantaged populations worldwide. The Sherpa people, located along the China and Nepal border, rely largely on the natural environment to access essential healthcare services. The region's ongoing economic and social developments threaten indigenous medicinal practices and biodiversity. However, there has been limited comprehensive investigation and documentation of traditional medicine and its associated knowledge in this region. Aim of the studyThe aims are to document the traditional medicinal knowledge of the Sherpa community, assess the conservation status of medicinal plants, and explore the historical factors that have influenced their traditional medicine practices. Material and methodsSemi-structured interviews with 78 Sherpa people were conducted in Chenthang Town, Xizang, China. Use reports (URs) was used to determine the most frequently mentioned medicinal plants or a specific ailment or disease category. The International Classification of Primary Care-2nd edition (ICPC-2) was used to transform the original records into an internationally unified classification. ResultsA total of 51 plant species, one fungus (Ophiocordyceps sinensis (Berk.) G.H.Sung, J.M.Sung, Hywel-Jones & Spatafora), two lichens (Flavopunctelia soredica (Nyl.) Hale and Parmotrema cetratum (Ach.) Hale), and four minerals were documented, resulting in 824 URs. Ranunculaceae had the most species (5 spp.). The most commonly used method for preparing medicinal substances was decoction (23 species, 40%). Oral application was the preferred route of administration for 81% (41 medicinal substances). Forty-four ailments across 14 ICPC-2 disease categories were documented. Respiratory (320 URs) and digestive (122 URs) categories are among the most common diseases. The top-five ailments were influenza (18 substances; URs = 227), injury blood/lymph/spleen other (11 substances; URs = 66), cough (10 substances; URs = 62), headache (7 substances; URs = 63), and abdominal pain/cramps general (6 substances; URs = 37). The most frequently reported medicinal substances were Panax pseudoginseng Wall. (URs = 128) and Neopicrorhiza scrophulariiflora (Pennell) D. Y. Hong (URs = 79). Two special therapies (hot spring therapy and dietary therapy) were described. In-depth ethnographic information on the livelihood and exchange history of Sherpa people were documented. A total of 25 species were sold, of which four species were listed as VU in the IUCN Red List (2023–1), six species were listed as VU, four species were NT, and one species was EN in the China Biodiversity Red list 2021. ConclusionThis study provides the first comprehensive documentation of the 58 traditional medicine substances and two special therapies (hot spring therapy and dietary therapy) used by the Sherpa people in Chenthang. Sherpa's medicinal knowledge has been shaped by historical interactions and contemporary trade practices. To better protect the biocultural diversity of the Himalayan region, priority should be given to the rapid assessment of medicinal plants, knowledge, and use status in this area.