Demethoxycurcumin (DMC) has anti-glioma effects in vitro and in subcutaneous xenotransplanted tumors. Our previous study confirmed that the molecule also has mild anti-glioma effects on orthotopic glioblastomas in vivo. In this study, we found that DMC-BH, a DMC analogue, exhibited more potent in vitro and in vivo activities than did DMC. DMC-BH was cytotoxic against various glioma cells including SHG-44, C6, U251, U87, A172 and primary glioma cells. DMC-BH activity was characterized by low acute toxicity and an appropriate pharmacokinetic profile. We evaluated the anti-tumor effects of DMC-BH in an ectopic xenograft model, an orthotopic glioblastoma xenograft model and a patient-derived tumor xenograft (PDTX) model. DMC-BH exhibited potent anti-tumor activity in both the ectopic xenograft and PDTX models. Indeed, bioluminescence measurements showed that DMC-BH exerted a significantly greater anti-tumor effect on orthotopic glioma growth than DMC. Immunohistochemical analysis revealed that DMC-BH inhibited expression of Ki67 and increased the incidence of TUNEL-positive cells. Western blotting showed that DMC-BH significantly decreased p-Akt and p-mTOR expression in orthotopic glioma tissues. These results suggest that the DMC analogue DMC-BH has potent anti-tumor properties that warrant further study.