Endometrial carcinoma (EC) is an epithelial malignant tumor that occurs in the endometrium. It is of great significance to explore new targets for improving the prognosis of endometrial cancer. Chikusetsusaponin Iva (CHI) is a plant compound extracted from Panacis japonica which has multiple biological activities, including anti-inflammation and anti-tumor effects. However, its possible effects on EC are unclear. Herein, we found that CHI inhibited EC cell proliferation and cell cycle, confirmed by colony formation and flow cytometry (FCM) assays. The results further confirmed that CHI stimulated the apoptosis of EC cells. Furthermore, we noticed that CHI treatment induced reactive oxygen species (ROS) in EC cells. In addition, it could suppress the Microtubule-Associated Protein Kinase (MAPK) pathway in EC cells, thereby affecting cell proliferation and apoptosis. Therefore, CHI could serve as a potential drug for EC treatment.