The interaction between individual amino acids and the surface of carboxylate-modified polystyrene nanoparticles in solution was studied using Saturation-Transfer Difference (STD)-Nuclear Magnetic Resonance (NMR). Individual amino acids were screened for nanoparticle binding using an STD-NMR experiment at a fixed saturation time, and STD buildup curves were measured for those amino acids that exhibited significant STD difference signals in the initial screening. The strongest STD effects were measured for protons of aromatic side chains, with relatively weaker effects observed for protons in long-chain aliphatic and positively charged side chains. This indicates that there are several modes of binding to these polystyrene nanoparticles: electrostatic attraction between the negatively charged surface of the carboxylate-modified polystyrene nanoparticle and positively charged amino acids, hydrophobic effects between long aliphatic side chains and the nanoparticle surface, and π-π interactions between aromatic amino acids and aromatic groups in styrene. This information can be used in future studies to predict and understand interactions between nanoparticle surfaces and specific amino acid residues in small peptides and proteins.