The Tibetan Plateau (TP) is one of the most challenging areas for human long-term settlement due to its extreme living environment. Understanding the relationship between human activities and environmental changes in this extreme environment is important and can provide a historical reference for adapting to future climate change. In this study, we took the Angren Basin in the southern TP as a case study to elucidate the relationship since Little Ice Age (LIA). Using fecal stanol in feces, lake and river surface sediments, surface soils, and sediment core, we found that specific indices S1 and S2 from the composition of coprostanol, epicoprostanol, 5β-ethylcoprostanol and 5β-ethylepicoprostanol can reflect changes in human population and herbivores, respectively. Through the comparison between environmental changes determined by grain size, elements, sedimentation rate, and other climate records, the relationship between human activities and environmental changes was interpreted. Our results indicate that: (i) during 1480–1820 CE, the fecal stanols in lake sediments mainly originated from livestock, and the human population was low. In contrast, during 1820–2021 CE, the proportion and flux of S1 have been continuously increasing, indicating significant population growth. (ii) During the middle LIA, the cold-dry climate inhibited the development of agriculture and farming. However, the increased precipitation during the late LIA promoted that development, resulting in an increase in human population and livestock in a short term. (iii) Since 1951, people have reclaimed wasteland and developed husbandry, leading to increased soil erosion. (iv) Over the past 40 years, with a warm-humid climate and good policy support, human activities, such as agriculture and husbandry, have rapidly increased, but soil erosion has declined in the recent 20 years due to good soil-water conservation efforts. This study sheds light on the relationship between human activities and environmental changes and provides insights into future climate change responses.