To test this hypothesis, we study the dynamics and solvent interactions of the PEGylated carbohydrate recognition domain of human Galectin-3 (Gal3C), a human β-galactoside-binding lectin that plays a significant role in cell adhesion 32 and potential cancer biology. Our investigation compared Gal3C conjugated with PEG molecules of two different molecular weights, 550 Da and 5 kDa, to investigate the relationship between the conjugated polymer and properties of the conjugated protein. Combining data from two-dimensional infrared (2D IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and molecular dynamics (MD) simulations, we compared the impact of the different-sized PEG molecules on the properties of conjugated Gal3C to test their effects on solvent accessibility and conjugate thermal stabilization. A unique strength of 2D IR spectroscopy is its ability to capture ultrafast molecular processes, which are leveraged to directly investigate protein-solvent interactions, solvent exposure, and the dynamics and organization of solvation networks surrounding proteins. We used 2D IR to investigate how PEGylation altered the backbone of conjugated Gal3C and investigate the impact of PEGylation on proteinsolvent interactions and solvent exposure. NMR spectroscopy provided complementary insights into the influence of conjugated PEG on the protein backbone at slower timescales and was also used to quantify the diffusion properties of PEGylated Gal3C. These measurements enabled us to correlate changes in solvation networks with the dumbbell and shroud models of protein-PEG interactions. MD simulations further complemented our experimental data by visualizing the conjugated polymer and providing a global characterization of solvation environments and backbone flexibility . Together, these integrated approaches enabled us to correlate polymer length with changes in the solvation network of the conjugated protein and its stability, providing mechanistic insights into the intentional design of protein-polymer conjugates with predictable properties.