It is widely reported that the overexpression of the C-C Motif Chemokine Receptor 2 (CCR2) has negative implications in neuroinflammatory diseases such as traumatic brain injury (TBI), although promising drugs to tackle this have been less forthcoming. As of 2016, only 2 drugs specifically targeting this receptor have made their way to market, with unsuccessful outcome unfortunately, suggesting that the search for more specific and precise ligands is utterly necessary. In this paper we hypothesized that by targeting Glu291, Met295, Trp98, Leu45 and Val189 amino acids, essential in the binding of CCR2 with C-C Motif Chemokine Ligand 2 (CCL2), the endogenous substrate, mitigates its activity in TBI. We used a pharmacophore model to screen for suitable ligands that may bind to CCR2, which returned 871 ligands. Docking and molecular dynamics results uncovered that two ligands (A102) and (A435) contained several of those important residues and showed a stability and compactness when in complex with CCR2, with these results confirmed by MMGBSA calculations with A102 recording a better interaction compared to A435. Finally, a PPI network was built to explore downstream signaling being regulated by both ligands in TBI, showing amyloid precursor protein (APP) as a key target and neuroactive-ligand receptor interaction (1.80E-27) the top functional annotated category. In conclusion, for the first time we report novel ligands A102 and A435 targeting CCR2 as a potential new pharmacological approach to target inflammation post-TBI.