Indigenous plant use-systems have evolved under, and constantly adapted to human and non-human impacts. In the last decades however, increasing socioeconomic and cultural transformations, including land-use change, outmigration, globalized markets, the introduction of new species, and climate change have led to a decreasing availability of indigenous resources, and are ultimately leading to a reduction of local use-knowledge. Participant observations, discussions, walks-in-the-woods, semi-structured interviews and informal meetings were carried out in 12 villages of far western Nepal between 2011 and 2015 to assess how sociocultural changes have affected the sustenance of indigenous systems and local biodiversity, when compared to studies carried out in the previous decades. Our findings show that there were no statistically significant differences in subject variable means, but differences were relatively important to plant parts-use and plant growth-forms (p = 0.183 and 0.088 respectively). Cissampelos pareira, Acorus calamus, Calotropis gigantea were found to have the greatest relative importance, whereas Ageratina adenophora, Melia azedarach, Carum carvi were most important based on use values. Among them, C. pareira and A. adenophora were introduced. The spatial distribution of species collected for medicine showed that all habitats were important for collection however, habitats close to villages were more favored. The use of non-indigenous and easily available species and more accessible habitats is becoming more prevalent as primary forests become increasingly overexploited, indigenous species become limited, and sociocultural cause of land use change expand. The utilization of indigenous and non-indigenous species and nearby habitats, although possibly affecting the quality of medicinal species, nonetheless reveals the dynamism of indigenous medicines as an adaptive asset mitigating human and non-human environmental changes.