 The study aimed to create mel-loaded polylactic co-glycolic acid, PLGA, nanoparticles, mel-PLGANPs, to alleviate carbon tetrachloride, CCl4, induced liver damage in male-sprayed dory rats. The prepared mel-PLGANPs were physically characterized and examined for antioxidant, anti-inflammatory, and anticoagulant effects before being used in vivo. Treatment with mel-PLGANPs ameliorated all-histopathological changes resulting from CCl4 administration reversed the elevated levels of liver function enzymes, inflammatory cytokines, and matrix metalloproteinases to their normal levels, and showed negative immunostaining for nuclear factor B, NFB, and C-reactive protein. The effective dose of NPs was 5 mg per kilogram, indicating a reduction in the required mel dose and its associated adverse effects. This article was authored by Alia Farid, Valina Michael, and Gihan Safwat.