Thrombotic events act as a critical factor that interferes with Cardiovascular Diseases (CVDs), and antithrombotic herbal medicine is a long-standing controversial issue. Although a dispute is involved in their clinical application, all parties unanimously agree that herbal products have been widely used in folk medicine, and their interactions with conventional drugs are of high concern. This study aims to investigate how antithrombotic herbal medicines interact with Western cardiovascular drugs on the molecular level by taking an example of the most frequently used herbal pair, Danshen−Chuanxiong (DS−CX), and to discover more scientific evidence on their potential herb−drug interactions. Network pharmacology (NP), as an analytical approach of a complex system, is used to visualize and compare target profiles of DS−CX and Western cardiovascular drugs, which can be applied to predict common herb-drug targets and to construct a solid context for discussing herb−drug interactions. These interactions are further validated by in vitro assays, while in vivo zebrafish model employed for evaluating an overall pharmacological efficacy of herbal pairs in specific combination ratios. The study finds that DS could react directly to the Western cardiovascular drug targets relevant to antithrombotic pathways (i.e., thrombin, coagulation factor Xa and cyclooxygenase-1), whereas CX could not react directly and can synergistically affect antithrombotic effects with DS in specific combination ratios. Moreover, it is indicated that DS−CX may generate wide biological functions by a complicated mechanism of “neuro−immune−metabolism/endocrine” (NIM), which can further cause multiple direct and indirect interactions with Western cardiovascular drugs. From the clinical perspective, herb−drug interactions should be given high attention, especially when multiple herbs are used simultaneously.