AbstractSiraitia grosvenorii, an economically important plant species with high medicinal value, is endemic to subtropical China. To determine the population structure and origin of cultivatedS. grosvenorii, we examined the variation in three chloroplast DNA regions (trnR‐atpA,trnH‐psbA,trnL‐trnF) and two orthologous nuclear genes (CHSandEDL2) ofS. grosvenoriiin 130 wild individuals (selected from 13 wild populations across its natural distribution range) and 21 cultivated individuals using a phylogeographic approach. The results showed three distinct chloroplast lineages, which were restricted to different mountain ranges, and strong plastid phylogeographic structure. Our findings suggest thatS. grosvenoriilikely experienced ancient range expansion and survived in multiple refuges in subtropical China during glacial periods, resulting in population fragmentation in different mountainous areas. Our results also demonstrated that wild populations in Guilin (Guangxi, China) share the same gene pool as cultivatedS. grosvenorii, suggesting that current cultivars were collected directly from local wild resources, consistent with the principles of “nearby domestication.” The results of this study provide insights into improving the efficiency ofS. grosvenoriibreeding using a genetic approach and outline measures for the conservation of its genetic resources.