Protein tyrosine phosphatase 1B (PTP1B) is a validated antidiabetic and anti-obesity target whose activity can be attenuated by small molecules engaging an allosteric cleft between helices α3/α7 beneath the Phe196/Phe280 “aromatic clamp.” Motivated by the tractability of terpene scaffolds, we evaluated artemisinic acid, dehydroabietic acid, and santonin as PTP1B allosteric inhibitors using an integrated in-silico pipeline. The 1T49 crystal structure was prepared and used for structure-based docking, followed by 200-ns explicit-solvent molecular dynamics (MD) and MM/PBSA end-point free-energy analysis. Docking located all three ligands in the α3/α7 pocket with predicted affinities of −7.6 (artemisinic acid), −8.1 (dehydroabietic acid), and −8.7 kcal·mol⁻¹ (santonin), reproducing the characteristic hydrophobic contacts to Phe196/Phe280 and polar interactions at the mouth (Asn193/Lys197/Glu200). MD indicated stable protein backbones for all complexes, while ligand mobility differentiated the series: the dehydroabietic-acid complex showed the lowest ligand RMSD and most persistent mouth hydrogen bonding; artemisinic acid was intermediate; santonin displayed greater early pose wandering despite favorable docking. MM/PBSA ranked dehydroabietic acid as the most favorable binder, followed by artemisinic acid, with santonin weakest—consistent with stronger van-der-Waals/packing and a smaller desolvation penalty for the abietane scaffold. Collectively, the data highlight deep hydrophobic burial against the aromatic clamp, plus one to two mouth-region polar contacts, as the key determinants of allosteric stabilization. Dehydroabietic acid emerges as a promising lead for optimization, with clear vectors to enhance potency while maintaining pocket complementarity. These findings support terpene-derived chemotypes as credible starting points for selective PTP1B allosteric inhibitor design.