Herbalism, rooted in traditional knowledge and regional practices, leverages plants as medicinal resources. India, with its vast biodiversity, harbors numerous untapped medicinal plants. This study focuses on the bioprospecting of two underexplored wild medicinal plants, Elsholtzia griffithii from Manipur and Smilax perfoliata from West Bengal, aiming to document their medicinal potential. We characterized metabolites in their crude methanolic extracts and explored their resistance to bacterial infections. Utilizing gas chromatography-mass spectrometry (GC-MS) analysis, 17 significant chemical compounds are identified, exhibiting physiological and pharmacological importance. Conducting disc-diffusion assays against E. coli, both plant extracts demonstrate antibacterial activity. Crude methanolic extracts of Smilax perfoliata and Elsholtzia griffithii showed a zone of inhibition of approximately 13 mm and 4 mm respectively. Additionally, molecular docking studies were conducted to evaluate the binding energy of the compounds to the E. coli receptors, DNA GyrB, and FabH and identify the receptor-ligand interactions. Among them, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine and Phthalic acid, dodecyl 2-methoxyethyl ester from Smilax perfoliata, and p-(dimethyl amino) benzaldehyde pyridine-4-carbonyl hydrazone from Elsholzia griffithii exhibit lower binding energy. The interactions between these 3 compounds and the receptors consisted of hydrogen bonding and hydrophobic interactions. Thus, it underscores the potential of compounds derived from these plants as inhibitors against gram-negative bacteria. Thus, our study unveils the ethnomedicinal properties of these wild plants, providing a comprehensive metabolite profile and paving the way for potential drug discovery.