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2-Deoxy-D-glucose (2-DG) is a glucose analog used as a promising anticancer agent. It exerts its effects by inhibiting the glycolytic energy metabolism to deplete cells of energy. The larval stage of Echinococcus relies on glycolysis for energy production. Therefore, in this study, we investigated the in vitro and in vivo efficacy of 2-DG against the larval stage of Echinococcus granulosus and E. multilocularis. 2-DG exhibited significant time- and dose-dependent effects against in vitro cultured E. granulosus protoscoleces and E. multilocularis metacestodes. A daily oral administration of 500 mg/kg 2-DG in E. multilocularis-infected mice effectively reduced the weight of metacestodes. Notably, the combination treatment, either 2-DG (500 mg/kg/day) + albendazole (ABZ) (200 mg/kg/day) or 2-DG (500 mg/kg/day) + half-dose of ABZ (100 mg/kg/day), exhibited a potent therapeutic effect against E. multilocularis, significantly promoting the reduction of metacestodes weight compared with the administration of 2-DG or ABZ alone. Furthermore, the combination significantly promoted apoptosis of the cells of metacestodes and inhibited glycolysis in metacestodes, compared with the administration of 2-DG or ABZ alone. In conclusion, 2-DG exerts an effective activity against the larval stage of Echinococcus. Thus, it may be a promising anti-Echinococcus drug, and its combination with ABZ may provide a new strategy for the treatment of echinococcosis in humans. Author summary: Echinococcosis is a serious but neglected helminthic zoonosis caused by the larval stage of Echinococcus granulosus and E. multilocularis. At present, clinical pharmacotherapy of echinococcosis, such as albendazole (ABZ) and mebendazole, has limited effectiveness. Thus, the development of novel therapeutic drugs for human echinococcosis is urgently needed. 2-Deoxy-D-glucose (2-DG) is a glucose analog used as a promising anticancer agent, and it exerts its effects by inhibiting the glycolytic energy metabolism to deplete cells of energy. Echinococcus in the host depends on glycolysis for energy production and glycolysis intermediates for other metabolic processes. Therefore, in this study, we investigated the efficacy of 2-DG against Echinococcus. 2-DG exerted an effective in vitro and in vivo activity against E. granulosus protoscoleces and E. multilocularis metacestodes, and the combination of this drug with ABZ further improved the therapeutic effect. Therefore, 2-DG can be developed as a promising anti-Echinococcus drug, and its combination with ABZ may provide a new strategy for the treatment of human echinococcosis in the future. [ABSTRACT FROM AUTHOR]