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This study was carried out to assess the pharmacodynamic properties of metformin and Vernonia amygdalina-loaded PEGylated-mucin matrices. Aqueous leaf extract of Vernonia amygdalina was obtained by cold maceration. Phytochemical analysis and LD50 determination were evaluated. Co-polymer matrices containing PEG and mucin in varying ratios were formulated. The particle size (PS), zeta potential (ZP), polydispersity index (PDI) and surface morphology were evaluated. The loaded drugs were evaluated for their blood glucose lowering potentials. Effects on haematological parameters, kidney electrolytes, liver enzymes, bilirubin and CD4+ cells were evaluated and were found very effective in glucose reduction and no negative effect on the other parameters studied. Phytochemical revealed several alkaloids, carbohydrates, tannins, saponins, flavonoids and glycosides, with an LD50 of 700 ± 13 mg/kg. The PDI, ZP, PS values ranges: (0.745 - 1.000), (-18.7- 23.2 mV), (82.4 - 484.5) respectively, the SEM were spherical and smooth. In conclusion, the results demonstrated that the formulation could be a possible alternative for the drug delivery system for the long-term treatment of diabetic.