Schiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy. The current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC 50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells. The Pd(II) complex displayed approximately the same IC 50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC 50 , 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels. It can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC 50 value. • New Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)− 1-(2-(p-tolyl)hydrazono)propan-2-one was synthesized. • The new Schiff base ligand contained metal ions which included Pd(II) and Zn(II) ions. • Zn(II) complex was the most effective anticancer drug. [ABSTRACT FROM AUTHOR]