This research aimed to contrast the metabolite compositions of four medicinal plants (Bidens pilosa, Lippia javanica, Syzygium cordatum, and Ximenia caffra) and assess their relevance for food preservation. Liquid chromatography-mass spectrometry results indicated 52 metabolites such as gallic acid, quinic acid, bergenin, coumaric acid derivative and citric acid etc., amongst the investigated medicinal plants. Specifically, B. pilosa had 15 identified metabolites along with six unknown polyphenols; L. javanica contained 16 known metabolites and four unidentified polyphenols; S. cordatum contained 19 metabolites and three unexplored polyphenols, whereas X. caffra had 19 identified metabolites and six unknown polyphenols. In the DPPH assay, S. cordatum demonstrated the strongest EC50 radical scavenging ability of 6.28 µg/mL, while X. caffra exhibited the least potency (21.68 µg/mL). Against Escherichia coli strains (ATCC 35218 and 25922), S. cordatum displayed the highest antibacterial activity (21 and 17.5 mm, respectively), while L. javanica showed the least (9.5 and 8 mm, respectively). L. javanica was potent against Enterococci faecalis (39 mm), and S. cordatum exhibited the most potent antibacterial activity against Staphylococci aureus (23.5 mm). The distinct antioxidant and antibacterial properties of these medicinal plants highlight their potential as natural preservatives in food industries, particularly in extending the shelf life of perishable foods and combating foodborne pathogens.