Punicalagin is the most bioactive polyphenols of pomegranate and has the potential to cure different ailments related to the CVS system. The current research work was envisioned to predict the targeting efficiency of punicalagin (PG) nanoparticles to the macrophages. For this, we select mannose decorated PLGA-punicalagin nanoparticles (Mn-PLGA-PG) and before formulation we predict the targeting efficiency of this nanocarrier by in-silico analysis. Authors initiated in-silico analysis on macrophage mannose receptor to be acquainted with the binding affinity. In-silico docking studies of macrophage mannose receptor and punicalagin showed binding interaction on its surface with a docking score of -4.00.PG interacts with hydrogen bonds to the charged residue ASP668 and GLY666 and polar residue GLN760 residue of Mn receptor. Mannose with a docking score of -5.811 and interacting with four hydrogen bonds to the mannose receptor of macrophage with two negatively charged residues GLU706, GLU719 also with two hydrophobic residues VAL716, PHE708 and in PLGA, it showed a -4.334-docking score. In trajectory analysis, the complex RMSD of macrophage while stabilizing the structure till 100ns, Mn receptor-PG found within the range of 4.6 Å. Initial fluctuation in RMSD noticed to 4.95 Åat 20ns which started stabilizing with timescale. In the total of 100ns, initially up to 40ns the PG (ligand) deviated to 1.2Å after 40ns, it is noted that the ligand RMSD was almost constant and started stabilizing and at 100ns it was 1.03Å. Findings depict that this nanocarrier could be a promising lead molecule to regulate the incidence of drug induced neutropenia.