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In this research, the possibility of using new suggested carriers (A) of vitamins (D3 and C) and amino acids (Leucine and Threonine) for diclofenac (Dc) drugs was addressed. Parameterization model 3 (PM3), unrestricted Harttre-Fock (UHF), unrestricted Density Functional Theory (U-DFT), and Docking have been used to calculate the reaction path of (O-A) bond rupture energies in diclofenac prodrugs (in vacuum). All were done at their optimize geometries by using Gaussian 09, Molecular Graphic Laboratory M.G.L. tools, Vina, BIOVIA (D.S.V.) and PyMol programs. The calculation involved the geometric structures, physical properties, lethal concentration (LC50), biological activity, and N.L.O. properties. Furthermore, the binding between Ribosomal protein S9 structure and the prodrugs in the liver were studied. Comparisons were made for the energies of the reactants, transition states, and products. The new carriers aim to improve the diclofenac drug's properties and provide new alternatives for the approved carriers. By examining the path of reaction of O-breakage energies, D3 and Threonine (Thr) represent a good prodrug due to their low heat of cracking (ΔHc), energy gap (ΔE), and activation energy (Ea#). At the same time, vitamin C and Leucine (Lue) showed a lower influence. In addition, LC50 showed theoretically that the maximum concentration of diclofenac carriers (Dc. A) was 9.290 × 10−10, 3.390 × 10−7, 6.762 × 10−7, and 1.125 × 10−6 M for Dc.D3, Dc.C, Dc.Leu, and Dc.Thr can be used, respectively. The order of the biological activity for the investigated carriers was Dc.D3 > Dc.C > Dc.Leu > Dc.Thr. The order of N.L.O. activity was Dc.D3 > Dc.Leu > Dc.C > Dc.Thr. In addition, the Autodock studies showed the ability of the suggested prodrugs to link with Ribosomal protein S9 structure in the liver for metabolism and producing an active drug (diclofenac acid). The suggested carriers were better than the common carriers (Na+ and K+) according to the binding energy.