At the molecular level, GS-Rh2 significantly reduced Gab2 expression and Akt2 phosphorylation in U251 cells and brain tumor tissues (<i>P</i> < 0.05).<h4>Conclusions</h4>GS-Rh2 inhibits migration and invasion of U251 glioma cells by decreasing Gab2 expression and Akt2 phosphorylation, suggesting that GS-Rh2 targets the Gab2/Akt2 signaling axis. Here, AKT2 is linked to central nervous system cancer.