Friction and wear are responsible for nearly 25% of global energy losses, underscoring the urgent need for efficient, sustainable lubricants. Glycerol has emerged as a promising green alternative to mineral and vegetable oils, offering low cost, favorable low-temperature performance, and significantly reduced friction. Despite its advantages, the molecular mechanisms underlying its superior lubricating properties are not fully understood. This project aims to develop a computational framework to investigate glycerol–water solutions confined between iron-based oxide surfaces under realistic thermodynamic and loading conditions. Large-scale molecular dynamics (MD) simulations using LAMMPS and NAMD, combined with density functional theory (DFT) and hybrid quantum mechanics/molecular mechanics (QM/MM) methods, will be employed to study shear-induced structural and chemical changes in the lubricant film. Steered non-equilibrium MD will simulate sliding at different pressures and shear rates, while ReaxFF MD will probe tribochemical processes on rough ferrous surfaces. By systematically varying glycerol concentration and introducing additives, we will explore the influence of composition on friction reduction, wear mitigation, and surface film formation. Ab initio MD will further clarify the chemical adsorption of glycerol degradation by-products. The integrated multi-scale approach will provide fundamental insight into the interplay of rheological effects, water formation, and tribochemical reactions in glycerol-based lubrication. These findings will inform the design of advanced, environmentally friendly lubricants with optimized performance, contributing to energy efficiency and reduced environmental impact.