Parkinson’s disease (PD) pathophysiology is associated with neuroinflammation and blood–brain barrier (BBB) dysfunction, yet the underlying mechanisms remain unclear. Microglia, a major source of insulin-like growth factor-1 (IGF-1) in the central nervous system, may influence BBB integrity during inflammation. In this study, we examined the effects of human IGF-1 (hIGF-1) on BBB cell injury induced by TNF-α and IFN-γ (TI) in vitro, using human microglial (HMC3) and brain microvascular endothelial (TY-10) cell lines. TI exposure increased pro-inflammatory markers (NLRP3, COX-2, pIκB) in HMC3 cells, elevated reactive oxygen species (ROS) production, and reduced TY-10 viability while altering structural proteins (decreased claudin-5, increased ICAM) and enhancing endothelial permeability. hIGF-1 treatment prevented ROS accumulation in HMC3 cells and upregulated claudin-5 in TY-10 cells, but did not rescue TI-induced permeability or viability loss in endothelial cells. These findings indicate that hIGF-1 exerts partial protective effects against inflammatory stress in these cells, reducing oxidative damage and modulating tight junction proteins, yet may be insufficient to fully counteract inflammation-induced functional deficits. Further work is needed to define the pathways involved and evaluate hIGF-1’s therapeutic potential in PD-related BBB impairment.