Non-wood forest products (NWFPs) derived from understory plants are attracting attention about sustainable forestry development. Geographical distribution and climate correlates of bioactive compounds are important to the regional management for the natural reserves of medical plants in forests. In this study, we collected Eleutherococcus senticosus individuals from 27 plots to map the special distribution of concentrations of eleutheroside B, eleutheroside E, and isofraxidin in forests of Northeast China. Compound concentrations in both aerial and underground organs were further detected for relationships with the average of 20-year records of temperature, precipitation, and relative humidity (RH). We found higher shoot eleutheroside B concentration in populations in northern and low-temperature regions (R = −0.4394; P = 0.0218) and in eastern and high-RH montane forests (R = 0.5003; P = 0.0079). The maximum-likelihood regression indicated that both RH (Pr > Chi-square, 0.0201) and longitude (Pr > Chi-square, 0.0026) had positive contributions to eleutheroside B concentration in roots, but precipitation had strongly negative contributions to the concentrations of eleutheroside E (Pr > Chi-square, 0.0309) and isofraxidin (Pr > Chi-square, 0.0014) in roots. Both geography and climate factors had effects on the special distribution of medical compounds in E. senticosus plants in natural populations in Northeast China. The management of NWFP plants at the regional scale should consider effects from climatic geography.