The rheological properties and zero-shear viscosity of water-based lubricants (WBLs) containing amino acid ionic liquids (AAILs) were investigated using both equilibrium (EMD) and non-equilibrium molecular dynamics (NEMD) simulations. We also performed experimental measurements to validate the simulations. The simulations demonstrated that adding AAIL additives to water increased both the shear viscosity and zero-shear viscosity. We added tetrabutylphosphonium (P4444) as a cation and three different amino acids, serine (Ser), lysine (Lys), or phenylalanine (Phe), as anions. We varied the AAIL concentration from 5 to 10 wt. % for tetrabutylphosphonium-serine (P4444-Ser) ionic liquid additives, showing that AAILs increased water viscosity by 68%–125%, depending on concentration. The P4444-Ser WBLs also exhibited a significantly higher first normal stress difference than water, meaning they could support more load in lubrication. The improved rheology persisted over a wide range of shear rates up to ∼1011 s−1. We have extracted full rheological parameters by fitting data into Cross, Carreau–Yasuda, and Eyring models, including zero-shear viscosity and critical shear rates of onset shear thinning. The experimental values of zero-shear viscosity were close to zero-shear viscosity results obtained from fitting NEMD results to these models, demonstrating the high fidelity of the molecular model. We explored the formation of hydration shells around amino acid anions as a marker for low friction behavior. These findings suggest that AAIL WBLs can be potentially low-friction and biodegradable lubricants in tribological applications.