Background: Chyangthapu-Phalaicha located in the northeastern Panchthar District, is a biodiversity hotspot in the Eastern Himalaya. The area is dominated by the Kirat indigenous community. The present study was conducted to document the knowledge of the ethnomedicinal uses and practices that exist in the area before the associated socio-cultural knowledge on biological diversity is lost. Methods: Ethnomedicinal data were collected through semi-structured questionnaires. Stakeholders meetings were organized for assessing the conservation issues in the sub-corridor. The importance of medicinal plant species was assessed using quantitative indices such as informant consensus factor, relative frequency of citation, relative importance, fidelity level and Rahman’s similarity index. Results: Altogether, 140 medicinal plant species from 68 families and 127 genera were reported, which were used to treat 12 health disorders categories. The dominant families were Asteraceae and Fabaceae which contributed eight species each. Fifty-five percent of the total medicinal plant species comprised of herbs. The most frequently used plant parts were underground parts (33%) and leaf (15%). The most common remedies preparation method was extract. Oral administration was the most common therapeutic mode (60%). Maximum informant consensus factor (0.96) was calculated for gastrointestinal disorders. The highest relative frequency of citation and fidelity level was observed for Swertia chirayita (0.83 and 100% respectively). Artemisia dubia depicted the highest relative importance (91.67). A thorough review of previous literature and analysis of field data revealed new therapeutic use reports for 41 ailments associated with 52 plant species. The Rahman similarity index was high with the studies in neighbouring areas, while it was low with the geographically distant studies. Conclusions: The ethnomedicinal study of the Chyangthapu-Phalaicha biological sub-corridor in the Kangchenjunga Landscape indicates that the area supports significant medicinal plants and associated traditional knowledge. The varied use of reported medicinal plants in the area indicates the need for their domestication, processing and phytochemical investigation, especially for those with high ethnobotanical indices.