Sini Decoction (SND) is the main prescription for treating Shaoyin disease in Zhang Zhongjing's Treatise on Typhoid diseases in Han Dynasty. It is composed of Aconitum carmichaeli Debeaux, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe. It has the effects of warming middle-jiao to dispel cold and revive the yang for resuscitation. Nowadays, it is mainly used in diseases in cardiovascular system, nervous system, digestive system and so on. In this paper, the effect and mechanism of the compatibility of Aconitum carmichaelii, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe in SND were described. The results showed that SND performed remarkbly on strengthening heart, promoting blood circulation as well as inhibiting cardiomyocyte apoptosis, anti-inflammatory and anti-hypothyroidism. The toxic effect of Aconitum carmichaelii was relieved by the combination of Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe. The mechanism of increasing efficiency and reducing toxicity after the compatibility of medicines in SND was discussed from the perspective of changes in biological effects and chemical compositions. In terms of biological effects, the mechanism of SND in treating heart failure, myocardial ischemia, myocardial hypertrophy and hypothyroidism and protecting cell injury were discussed. As to chemical composition changes, most studies have compared the changes of main components in Aconitum carmichaelii, Glycyrrhiza uralensis Fisch ex DC and Zingiber officinale Roscoe with the whole prescription, drug pair and single Decoction, which further confirmed the effect of Glycyrrhiza uralensis Fisch ex DC on the detoxification of Aconitum carmichaelii and the significance of compatibility efficiency of SND. For the application of differently processed varieties of Aconitum carmichaelii in SND, the treatment of different diseases has siginificant tendencies and differences in the selections of Aconitum carmichaelii processed varieties. This paper will lay a foundation on clarifying the mechanism of drug compatibility of SND and in the future, provide a reference for the proper selection of differently processed products of Aconitum carmichaelii in SND in order to exert better effects in clinical practices.