Cornus officinalis Siebold & Zucc. is an important Chinese herbal medicine with traditional clinical applications, a long history of cultivation and high economic value in China. C. officinalis is distributed mainly in the Shaanxi, Henan, and Zhejiang provinces of China, which are also historically the main production areas, and which still provide 90% of the medicinal material of this species for the contemporary market. In this study, we investigated the main germplasm resources of C. officinalis across its distribution, based on fruit morphology, the concentrations of selected medicinally active ingredients, and molecular population genetic analysis. The results indicated that the C. officinalis populations sampled had abundant variation in fruit morphology and chemical component content, and showed high genetic diversity, as revealed by microsatellite markers. Clustering results based on morphology, active ingredient concentration and microsatellite markers supported the idea that populations from Zhejiang province were distinct from those in Shaanxi and Henan. The fruit and molecular data suggested that the Shaanxi and Henan populations were mixed, which could be attributed to their close geographical distance and frequent germplasm exchange. Most of the C. officinalis populations had relatively weak genetic differentiation from others sampled, and most of the individuals sampled showed extensive admixture. We suggest that artificial gene flow caused by intensive cultivation and widespread trading is responsible for the observed admixture of genetic components and blurred genetic boundaries between C. officinalis populations, especially in the Shaanxi and Henan populations. We also propose some suggestions for the efficient utilization and conservation of C. officinalis germplasm. These findings provide valuable information on the genetic resources of C. officinalis and offer guidelines for breeding programs and scientific management of C. officinalis.