We present a detailed investigation on the effects of water diffusion at the different interfaces of gold-graphene plasmonic sensors on the propagation of the supported surface plasmon polaritons (SPPs). The substrate/metal interfacial chemical reactions are investigated by monitoring the full width at half-maximum of the SPR reflectivity curve. Although protection by single-layer graphene (SLG) grown by chemical vapor deposition inhibits the chemical reactions happening at the metal-dielectric interfaces, SPR experimental results confirm that water diffusion paths through the borders of graphene domains are still present into the plasmonic sensors. Density functional theory calculations show that the doping level of SLG after the transfer on gold as well as interfacial charge transfer can be tuned in the presence of water molecules. On these bases, we propose a simplified effective medium approach for heterogeneous metal-carbon interfaces, where the interaction between the surface atomic layers of the gold thin film, water molecules, and the SLG induces the creation of an extended charge density difference region crossing the Au/H2O/SLG/H2O heterointerface. The latter is modeled as an ultrathin effective medium with a thickness and extraordinary optical susceptivity and conductivity that are different from those of the free-standing graphene. In this context, the extraordinary refractive index and thickness of the graphene-gold effective medium are measured in the near-infrared on the low-damping SPR platforms by applying the two-medium SPR method. The results are coherent with graphene n-doping in water environment, showing that the optically excited electrons along the extraordinary axis have a substantial bonding character and that the enhancement of the sensitivity of the gold-graphene plasmonic sensors is not related to a shift in the plasma frequency of the metal layer but to the changes in the extraordinary polarizability of graphene. The research highlights the importance of the SLG-substrate and SLG-environment interactions in graphene-protected plasmonics and optoelectronics.