Nowadays, knowledge about the uses of medicinal plants is growing exponentially, and in order to conserve and valorize this knowledge, the European Union has set up multiple regulations to control their usage by the population. In this framework, this work is based on EU regulations to elaborate a new phytomedicine for intestinal comfort. The phytomedicine subject of elaboration is under the category of Traditional Use Herbal Medicine Products (TUHMPs), containing plants of approved medicinal use of at least 30 years, including 15 years in the European Union (Myrtus communis L. leaves (MC), Pimpinella anisum L. seeds (PA) and Carum carvi L. (CC) fruit). The EU pharmacopeia and monographs recognize the individual effect of each plant selected, and this work aims to study their combined effect using a mixture design. Acetic acid-induced writhing test in mice is used to study the efficacy of the mixture as pain relief and for intestinal comfort. According to the test result, the individual, binary and ternary combination were very effective compared to negative and positive control approving by that the synergy between the plants. Following the mixture design analysis, the best formulation was a ternary combination with different ratios (MC: 45%, PA: 52% and CC with 3%). The predicted formulation was studied after that and approved by the test result. This work provided a practical way to establish new phytomedicines within the EU and could be a model for new outcoming phytomedicine in the market.