Purpose <p>The purpose of this review study is to investigate the effect of curcumin on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in various diseases. Curcumin, the main compound found in turmeric, has attracted a lot of attention for its diverse pharmacological properties. These properties have increased the therapeutic potential of curcumin in chronic diseases such as cardiovascular disease, Type 2 diabetes, obesity, non-alcoholic fatty liver disease, kidney disease, and neurodegenerative diseases. One of the main mechanisms of the effect of curcumin on health is its ability to modulate the PI3K/Akt signaling pathway. This pathway plays an important role in regulating vital cellular processes such as growth, cell survival, metabolism, and apoptosis. Disruption of the PI3K/Akt signaling pathway is associated with the incidence of several diseases.</p> Methods <p>Electronic databases including PubMed, Google Scholar, and Scopus were searched with the keywords “phosphoinositide 3-kinase” AND “protein kinase B “AND “curcumin” in the title/abstract. Also, following keywords “non-alcoholic fatty liver disease” AND “diabetes” AND “obesity” AND “kidney disease” and “neurodegenerative diseases” was searched in the whole text.</p> Results <p>Research indicates that curcumin offers potential benefits for several health conditions. Studies have shown it can help regulate blood sugar, reduce inflammation, and protect the heart, kidneys, and brain.</p> Conclusion <p>This protective effect is partially achieved by regulating the PI3K-Akt survival pathway, which helps improve metabolic disorders and oxidative stress. By examining how curcumin affects this vital cell pathway, researchers can discover new treatment strategies for a range of diseases.</p>