Medicinal plants are an essential component of traditional healthcare systems in Nepal, particularly among rural and indigenous communities. This study documents and analyzes the ethnobotanical knowledge and use patterns of medicinal plants among three ethnic groups—Bankaria, Newah, and Tamang—in Makawanpur district, Central Nepal. Data were collected through interviews with 165 informants across five locations differing in altitude. Botanical voucher specimens were gathered for accurate plant identification. Quantitative indices including Informant Consensus Factor (ICF) and Relative Frequency of Citation (RFC) were used to assess plant use patterns, and statistical analyses examined correlations with ethnicity, gender, age, and geographic location. A total of 189 medicinal plant species were identified, primarily sourced from forests (130 spp.) and fallow lands (49 spp.), with limited cultivation in homegardens. Digestive, skin, and respiratory ailments were most frequently treated, reflected in high ICF values. Urtica dioica, Terminalia chebula, and Swertia chirayita emerged as the most cited species. While gender had no significant impact on medicinal plant knowledge, location and age were influential: rural and lowland respondents, as well as older individuals, demonstrated higher knowledge levels. The Newah group reported significantly fewer uses compared to Bankaria and Tamang participants. Findings highlight that medicinal plant knowledge is shaped by both socio-cultural and ecological factors. Comprehensive ethnobotanical documentation across diverse communities is therefore vital. The study also identifies key plant species with high local relevance, suggesting their prioritization for further pharmacological validation and potential domestication.