Introduction: Garcinia cowa (Clusiaceae) is popular among integrative medicine in several communities.This study undertook to evaluate the anti-proliferative activity on cancer cells and its cytotoxic effect on normal cells. Here we are reporting for the first time the metabolomic profiling of G. cowa leaf. Methods: Anti-proliferative potential of ethyl acetate and methanol extract of Garcinia cowa leaf assessed by MTT assay. Metabolomic profiling obtained by GC/ MS analysis. Nuclear morphology visualized by DAPI staining. Caspase activation analysed through spectrophotometric assay. Results: The study reveals, that the methanolic extract is more potential in inducing anti-proliferative activity than ethyl acetate extract. Robust anti-proliferative activity of the methanolic extract evidenced in lung cancer cell line, A549 followed by MCF–7, HepG2, MOLT – 4, MDA-MB-468 cells.The anti-proliferative effect was negligible in normal PBMC. Further, a dose-dependent increase of nuclear fragmentation visualized in A549 cells treated with the methanolic extract. Post methanolic extract treatment upregulation of caspase-3 and caspase-9 also evidenced in A549 cells. GC/MS analysis revealed the presence of phytoconstituents of different phytochemical groups comprising of 3.45% diterpenoid, 5.45% triterpenoid, 11.24% steroid, 2.03% phytosterol, etc. in methanol extract, as well as 4.53% diterpenoid, 2.88% triterpenoid, 1.09% steroid, 2.11% phytosterol, etc. in ethyl acetate extract with considerable biological importance. Conclusion: This is the maiden report of the metabolomic profiling of leaf extracts of Garcinia cowa which possess a good repository of potentially bioactive molecules that holds a great promise as a future therapeutic agent in combating lung cancer. © 2021 Phcogj.Com.