Zehneria scabra is a perennial climbing herb used by Ethiopian traditional medicine practitioners. The study aimed to detect phytochemicals, assess antibacterial activities, and analyse the chemical constituents of its leaf extract using GC–MS and FTIR techniques. Phytochemical analysis revealed terpenoids, alkaloids, flavonoids, phenols, tannins, and saponins. Significant antibacterial activity was observed against Staphylococcus aureus and Escherichia coli at low concentrations (0.05 mg), particularly inhibiting E. coli. Quantitative phytochemical analysis showed that eight compounds make up almost ¾ part of the GC–MS chromatogram. These main constituents were 13-Octadecenal (17.77%), Valerenic acid (16.19%), 7-Acetyl-6-ethyl-1,1,4,4-tetramethyltetralin (8.96%), (Z, Z, Z)-9,12,15-Octadecatrienoic acid, methyl ester (7.35%), Neophytadiene (7.11%), 9,12-Octadecadienoic acid (Z, Z)-, methyl ester (5.45%), Hexadecanoic acid, methyl ester (5.08%), and 2-Isopropylidene-3-methylhexa-3,5-dienal (5.06%). FT-IR analysis also confirmed the presence of alkanes, alcohols, phenols, aldehydes, ketones, esters, and aromatic functional groups. Overall, these identified compounds from Z. scabra hold promise for developing innovative antibacterial drugs.