Curcumin, a polyphenol from turmeric, has shown significant anti-cancer potential by modulating key signaling pathways, particularly the PI3K/Akt pathway, which is crucial in cancer progression, survival, and resistance to therapy. This review discusses curcumin's effects on various cancers, including glioblastoma, lung cancer, breast cancer, prostate cancer, colorectal cancer, thyroid cancer, and leukemia, through its regulation of the PI3K/Akt pathway. Curcumin inhibits PI3K/Akt signaling by downregulating key mediators such as Akt, mTOR, and growth factors, leading to reduced tumor growth, metastasis, and cell survival. It also induces apoptosis, autophagy, and paraptosis in cancer cells, while sensitizing them to chemotherapy and radiotherapy. Despite its promising therapeutic effects, curcumin's poor bioavailability and pharmacokinetic profile limit its clinical application. Recent advances in delivery systems, such as nanoparticles and liposomes, aim to enhance curcumin's bioavailability and efficacy. The PI3K/Akt pathway is frequently dysregulated in cancers, with mutations in PIK3CA, PTEN, and AKT contributing to its activation. Curcumin's ability to target this pathway offers a promising strategy for cancer treatment, particularly in overcoming drug resistance and improving clinical outcomes. Further research is needed to fully understand curcumin's mechanisms and optimize its therapeutic potential.Curcumin, a polyphenol from turmeric, has shown significant anti-cancer potential by modulating key signaling pathways, particularly the PI3K/Akt pathway, which is crucial in cancer progression, survival, and resistance to therapy. This review discusses curcumin's effects on various cancers, including glioblastoma, lung cancer, breast cancer, prostate cancer, colorectal cancer, thyroid cancer, and leukemia, through its regulation of the PI3K/Akt pathway. Curcumin inhibits PI3K/Akt signaling by downregulating key mediators such as Akt, mTOR, and growth factors, leading to reduced tumor growth, metastasis, and cell survival. It also induces apoptosis, autophagy, and paraptosis in cancer cells, while sensitizing them to chemotherapy and radiotherapy. Despite its promising therapeutic effects, curcumin's poor bioavailability and pharmacokinetic profile limit its clinical application. Recent advances in delivery systems, such as nanoparticles and liposomes, aim to enhance curcumin's bioavailability and efficacy. The PI3K/Akt pathway is frequently dysregulated in cancers, with mutations in PIK3CA, PTEN, and AKT contributing to its activation. Curcumin's ability to target this pathway offers a promising strategy for cancer treatment, particularly in overcoming drug resistance and improving clinical outcomes. Further research is needed to fully understand curcumin's mechanisms and optimize its therapeutic potential.