Cancer remains a significant global health issue, and the search for new treatment options has led to increased interest in natural compounds. Curcumin, a polyphenol derived from turmeric, has been extensively studied for its anti-inflammatory, antioxidant, and anti-cancer properties. This review focuses on the role of curcumin in regulating the PI3K/Akt signaling pathway, which is a key target in cancer therapy due to its involvement in cell growth, proliferation, and survival. Curcumin has been shown to inhibit the PI3K/Akt pathway in various cancers, including glioblastoma, prostate cancer, breast cancer, head and neck cancers, and leukemia. The mechanism of action involves targeting key mediators such as growth factors, protein kinases, and cytokines. Additionally, curcumin has been found to induce apoptosis, autophagy, and paraptosis, and to sensitize tumor cells to chemotherapy and radiotherapy. The review highlights the therapeutic potential of curcumin in different malignancies, emphasizing its ability to target the PI3K/Akt pathway and improve clinical outcomes. Despite the promising results, challenges such as poor bioavailability and the need for novel delivery systems remain. Future research should focus on optimizing curcumin's delivery and enhancing its biological effects to overcome these limitations.Cancer remains a significant global health issue, and the search for new treatment options has led to increased interest in natural compounds. Curcumin, a polyphenol derived from turmeric, has been extensively studied for its anti-inflammatory, antioxidant, and anti-cancer properties. This review focuses on the role of curcumin in regulating the PI3K/Akt signaling pathway, which is a key target in cancer therapy due to its involvement in cell growth, proliferation, and survival. Curcumin has been shown to inhibit the PI3K/Akt pathway in various cancers, including glioblastoma, prostate cancer, breast cancer, head and neck cancers, and leukemia. The mechanism of action involves targeting key mediators such as growth factors, protein kinases, and cytokines. Additionally, curcumin has been found to induce apoptosis, autophagy, and paraptosis, and to sensitize tumor cells to chemotherapy and radiotherapy. The review highlights the therapeutic potential of curcumin in different malignancies, emphasizing its ability to target the PI3K/Akt pathway and improve clinical outcomes. Despite the promising results, challenges such as poor bioavailability and the need for novel delivery systems remain. Future research should focus on optimizing curcumin's delivery and enhancing its biological effects to overcome these limitations.