Novel chitosan oligosaccharide derivatives with amphiphilic functional groups were prepared, and the abilities of these derivatives to protect P110 steel in a CO2-saturated solution with 3.5 wt.% NaCl were evaluated. FTIR and 1H-NMR demonstrated that the amphiphilic groups were successfully grafted onto the chitosan oligosaccharide molecules. Evaluation by weight loss, AFM and SEM demonstrated that the novel derivatives, PHC and BHC had good corrosion inhibition effects with respect to P110 steel in a saturated CO2 salt solution. Inhibition efficiency increased as inhibitor concentration increased. At PHC and BHC concentrations of 100 mg/L, inhibition efficiencies were 85.70% and 88.59%, respectively. Surface analysis experiments (EDX and contact angle) demonstrated that PHC and BHC successfully adsorbed to the steel surface and changed the hydrophilic and hydrophobic nature of the steel surface. Potentiodynamic polarization results showed that both PHC and BHC were mixed-type inhibitors but mainly acted on the cathode. Quantum chemical theoretical calculations of PHC and BHCshowed that the interaction between BHC and iron is stronger than PHC. BHC also showed greater inhibition efficiency than PHC when tested via the weightlessness method, EIS and potentiodynamic polarization measurements demonstrating consistency between the experimental and theoretical results.