Though Traditional Chinese Medicine (TCM) has long been playing a significant role in the maintenance of health for people in Asia as well as many other places, the mechanism of its action still remains ambiguous for most of the plants used in TCM, such as Eucommia ulmoides Oliv., a kind of herb that is widely used to help regulate hypertension and the immune system nowadays. However, its functioning mechanism is still unknown. Thus it is necessary to exploit the mechanism of Eucommia ulmoides Oliv. A systems pharmacology approach combining drug-likeness evaluation, oral bioavailability prediction, multiple drug targets prediction as well as network pharmacology techniques has been used. This comprehensive systematic approach helps successfully to identify 41 candidate compounds contained in Eucommia ulmoides Oliv. while 39 potential targets hit by these ingredients and helps to uncover the synergistic mechanism of action on a systematic level. Our work successfully explains the mechanism of the efficiency of Eucommia ulmoides Oliv. for the treatment of hypertension and enhancing immune. These results not only provide a new insight for the understanding of the chemical and pharmacological basis of Eucommia ulmoides Oliv., but also provide an efficient way for drug discovery from herbal medicine. Display omitted