Chemotherapy is one of the main therapeutic modalities for cancer patients. Cisplatin (CDDP), as one of the first-line drugs, is of great importance in the chemotherapy of various tumors. However, a significant percentage of cancer patients are resistant to CDDP treatment. Due to the CDDP side effects on normal tissues, the diagnosis of CDDP resistance is required to suggest the most efficient therapeutic strategies for cancer patients. Several molecular mechanisms and signaling pathways are associated with CDDP response. The PI3K/AKT signaling pathway has a pivotal role in the transmission of extracellular signals into the cells to regulate various pathophysiological processes such as cell proliferation, migration, and drug resistance. In the present review, we summarized all of the studies which have been reported on the role of PI3K/AKT pathway in regulation of CDDP response. It was shown that the PI3K/AKT pathway is mainly involved in CDDP response in lung, ovarian, and gastrointestinal cancers. It was also observed that the non-coding RNAs have a key role in CDDP response by regulation of PI3K/AKT pathway. This review paves the way for suggesting a PI3K/AKT-related panel marker for the prediction of CDDP response in different cancer patients.