Objective To explore the action and possible mechanism of isomangiferin suppression to malignant glioma cells U251. Method U251 cells were cultivated routinely and then treated with bergenin. Next, the cells were detected by MTT assay to test the viability, plate clone formation assay to test colony formation ability, transwell small chamber migration and invasion assay to test longitudinal migration and invasion ability, scratch healing assay to test lateral migration ability, and western blot to test the change of PTEN-PI3K-AKT-mTOR pathway. Results After the cells treated with certain concentrate gradient isomangiferin, the U251 cell viability declined in a time and concentration dependent way by MTT assay, the colony formation ability of U251 cells was suppressed in a concentration dependent manner by plate clone formation assay, the longitudinal invasion and migration ability were inhibited in a concentration dependent manner through transwell chamber migration and invasion assay, and simultaneously the lateral migration ability was also restrained in same way. Subsequent western blot assay found the expression of PTEN was upregulated, but the phosphorylated PI3K, AKT and mTOR expression quantity declined in a concentration dependent way. Conclusion Isomangiferin can inhibit the malignant biological behavior of malignant glioma cells and the mechanism have relation with regulating PTEN-PI3K-AKT-mTOR pathway.