Molecular weight reduction of natural rubber (NR) with hydrogen peroxide (H₂O₂) oxidizing agent is limited in biphasic water-toluene systems that is attributed to mass transfer. In this work, CO₂ was applied to the (aqueous H₂O₂)-(toluene-NR) systems with the objective of improving reaction efficiency. Experiments were performed on the reaction system with CO₂ at 12 MPa and at reaction temperatures and times of 60°C–80°C and 1 h–10 h to evaluate the reaction kinetics. CO₂ could enhance the NR molecular weight reduction by lowering the activation energy (from 121 kJ·mol⁻¹ to 38 kJ·mol⁻¹). The role of CO₂ in the reaction system seems to be the formation of oxidative peroxycarbonic acid intermediate and promotion of mass transport due to the reduction in the toluene-NR viscosity and interfacial tension. The epoxidized liquid NRs (M̅_n=4.9×10³ g·mol⁻¹) obtained from NR molecular weight reduction was further processed to prepare hydroxyl telechelic NR (M̅_n=1.0×10³ g·mol⁻¹) and biobased polyurethane.