BACKGROUND AND OBJECTIVE: Lung cancer stands as the leading cause of cancer-related fatalities worldwide. While chemotherapy remains a crucial treatment option for managing lung cancer in both early-stage and advanced cases, it is accompanied by significant drawbacks, including severe side effects and the development of chemoresistance. Overcoming chemoresistance represents a considerable challenge in lung cancer treatment. Amlodipine cytotoxicity was previously demonstrated and could make lung cancer cells more susceptible to chemotherapies. This research aims to examine the metabolomics changes that may occur due to amlodipine's anticancer effects on non-small cell lung cancer (NSCLC) cells. METHODS: Amlodipine's effects on A549 and H1299 NSCLC were evaluated using a colorimetric MTT assay, a scratch wound-healing assay and Matrigel invasion chambers to measure cell viability, cell migration and cell invasion. Ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) was used for the untargeted metabolomics investigation. RESULTS: Our study revealed that amlodipine significantly reduced proliferation of cancer cells in a dose-dependent fashion with IC CONCLUSION: The present study illustrates the anticancer effects of amlodipine on lung cancer proliferation, migration, and invasion in vitro and enhance our understanding of how amlodipine exerts its anticancer potential by casting light on these mechanisms.