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Curcumin (CUM) can regulate the malignant behavior of glioblastoma (GBM). This study investigates whether CUM suppresses GBM progression by inducing cuproptosis via the AKT/Wnt/β-catenin signaling pathway. Optimal curcumin concentrations were determined using the MTT assay. A172 and U251 cells were treated with CUM, AKT inhibitor MK-2206, Wnt inhibitor LGK974, and Elsm-Cu (Elesclomol + CuCl2). Cell proliferation, migration, invasion, and apoptosis were assessed using carboxyfluorescein succinimidyl amino ester staining, scratch assays, Transwell assays, and flow cytometry, respectively. MitoSOX fluorescence, Seahorse metabolic analysis, immunofluorescence, Cu²⁺ detection, and Western blotting were used to evaluate mitochondrial oxidative stress and cuproptosis. The AKT/Wnt/β-catenin axis was analyzed using a TCF/LEF1 reporter kit and western blotting. A GBM xenograft model was established, and CUM was administered by gavage for five weeks. CUM effects on tumor growth, cuproptosis, and AKT/Wnt/β-catenin pathway protein expression were evaluated. Cells were treated with 10 µM and 20 µM CUM in vitro. CUM treatment reduced proliferation, migration, and invasion, while promoting oxidative stress and cuproptosis. CUM also suppressed Wnt/β-catenin signaling activity. Pathway inhibition increased reactive oxygen species (3.7-fold) and Cu²⁺ (3.1-fold) levels, and decreased dihydrolipoamide acetyltransferase expression, thereby restraining malignant behavior. In nude mice, CUM significantly reduced tumor growth, promoted cuproptosis, and inhibited AKT/Wnt/β-catenin axis activation. Our results indicate that CUM suppresses AKT/Wnt/β-catenin signaling, promotes cuproptosis, and interferes with GBM progression.