<p>Some conventional drugs are swiftly accessible and poorly soluble in the body. Although it is less soluble and accessible, silymarin, a well-known antioxidant drug, is used to treat several ailments. It is integrated into green-designed <i>Fagonia cretica</i> extract (FCE) based on PEGylated-Sily@ZnFe₂O₄ in this work to enhance these characteristics. UV–visible spectrometry, X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and zeta potential analysis were all used to thoroughly analyze the nanocomposites. As a result, ZnFe₂O₄ nanocomposites (NCs) produced nanostructures with an average crystal size of 7.66&#xa0;nm, whereas PEGylated-Sily@ZnFe₂O₄ nanodrug produced with an average crystal size of 25.38&#xa0;nm. The ZnFe₂O₄ NCs produced nanostructures with an average grain size of 332&#xa0;nm and 504&#xa0;nm, respectively as deduce by SEM analysis. Silymarin was estimated to have a loading efficiency of 27.39% into ZnFe₂O₄ NCs. To examine the produced nano-drug’s in vivo antioxidative capacity in the liver in comparison to pure silymarin, albino rats intoxicated with CCl₄ were administered different dosages of 500 and 1500 μg/kg body weight. In hepatic tissue, CCl₄ increased ROS and TBARS and lowered SOD, POD, and CAT levels, causing DNA damage that was mitigated subsequently by PEGylated-Sily@ZnFe₂O₄. In a rat model of CCl₄-induced hepatotoxicity, the in vivo assessment experiments showed that the synthesized PEGylated-Sily@ZnFe₂O₄ efficiently displayed a hepatoprotective effect by mitigating cellular abnormalities caused by CCl₄ toxication. Additionally, the PEGylated-Sily@ZnFe₂O₄ was shown to reduce the degree of DNA damage in the COMET experiment. In contrast to the traditional drug silymarin, the PEGylated-Sily@ZnFe₂O₄. Nanocomposites may be useful in the future in sustaining a variety of tissues by lowering oxidative stress.</p>