Untargeted metabolomics identified metabolic alterations, while DARTS proteomics screened for potential TPL-interacting proteins.<h4>Results</h4>TPL significantly inhibited NSCLC cell proliferation and induced metabolic alterations characterized by glycolytic suppression (HK2 downregulation) and concurrent disruption of mitochondrial oxidative phosphorylation (OXPHOS)-associated proteins. Here, HK2 is linked to non-small cell lung carcinoma.