Ziziphus mauritiana is a medicinal plant commonly used in conventional therapies since it has health-beneficial effects, as it is rich with many biologically active compounds. However, scientific research on this plant’s metabolite profile is insufficient. The goals of this study are to establish chemical profiles of Z. mauritiana leaves that were extracted using a variety of polarity solvents. 1H NMR-metabolomics was employed to investigate the correlation between chemical markers and anti-Vibrio activities. A portion of the powdered sample of Z. mauritiana was extracted using different solvent systems (hexane, chloroform, acetone, and 70% (v/v) ethanol). The profiles of metabolites in each extract obtained were determined by NMR spectroscopy. The correlation between the identified metabolites and anti-Vibrio properties of Z. mauritiana was interpreted using the metabolomics approach. The Z. mauritiana extracts were successfully clustered using principal component analysis according to their metabolite profiles. Acetone and 70% (v/v) ethanol were determined to have good extraction efficiency. The anti-Vibrio activity was shown to be highly correlated with the polar metabolites of the 70% (v/v) ethanol extract in the partial least squares analysis. The 70% (v/v) ethanol extracts exhibit a more diverse spectrum than the other extracts, with a total of 42 metabolites that include carbohydrates, amino acids, organics, and fatty acids. The rapid examination of the metabolite composition of Z. mauritiana in relation to its various solvent extractions with a specific anti-Vibrio biological activity has been facilitated by the implementation of NMR-metabolomics.