An in-depth understanding of the relationship between anthropogenic activity and climate change under extreme climate conditions could provide a scientific basis and historical reference for coping with future climate change properly. This understanding is also crucial for ensuring the sustainable development of ecology, environment, economy, and society. Here, fecal stanols in the Xiada Co sediment core on the western Tibetan Plateau (TP) were used to reconstruct local human and ruminant populations over the past 4700 years. Climate data based on brGDGTs and X-ray fluorescence (XRF) data in the same sediment core, along with relevant documentary and archaeological evidence from the TP, were also compiled to investigate the relationship between human activity and climate change in the western TP during the late Holocene. Our analysis suggests that the change in human and ruminant populations in the Xiada Co basin was likely influenced by regional climate change, fluctuations in the lake level, and social factors. From 4700 to 2900 cal yr BP, the populations were relatively high due to the warm and humid climate compared to the period of 2300–0 cal yr BP. During 3400–2900 cal yr BP, the basin experienced the highest population density. This could be attributed to the combination of a relatively warm and humid climate, the introduction of cold and dry-tolerant crops like barley, and the introduction of livestock such as sheep/goat and cattle into the western TP. Between 2900 and 2450 cal yr BP, the increased lake levels and frequent level changes likely caused significant population declines. From ∼1000 to 300 cal yr BP, temperature appeared to have a stronger influence on human and ruminant population change compared to lake level and precipitation. Notably, around 300 cal yr BP, the basin experienced the smallest human and ruminant populations due to the extremely cold and dry climate, as well as frequent conflicts between Guge and Ladakh. From 0 cal yr BP onward, there was a notable increase in both human and ruminant populations in the Xiada Co basin, which aligns with the data on populations in Rutog county, Nagri prefecture. Furthermore, the significant rise in the levels of ruminant fecal stanols suggests a shift in the primary domesticated ruminant species after ∼1250 cal yr BP, with sheep/goat becoming the dominant livestock. This is supported by absolute concentration of fecal stanols in local contemporary animal feces and relevant archaeological evidence from the western TP. This study confirms the use of fecal stanols as a valuable tool for reconstructing ancient human activities on the western TP.