The unique properties of compressed CO2, including its low cost, nontoxicity, easily tunable solvent strength, and favorable transport properties, make it an environmentally attractive alternative to volatile organic solvents. Suitable surface-active species can be utilized to realize the full potential of clean, CO2-based technologies, by helping to overcome the low solubility typically associated with many solutes of interest in CO2. In this work we synthesize and investigate the interfacial activity of a series of nonionic amphiphiles with a biocompatible and biodegradable CO2-phile at both the CO2-water (C vertical bar W) and CO2 Water-solid (C vertical bar W vertical bar S) interfaces. We developed a high-pressure pendant drop tensiometer and contact angle goniometer that allows us to measure both tension and contact angle in tandem. The tension of the C vertical bar W interface was measured in the presence of the lactide (LA)-based surface active agents with varying molecular weight and hydrophilic-to-CO2-philic ratios. Emulsion studies with an optimum balanced surfactant were performed. The contact angle of water droplets against a silane-modified (hydrophobic) substrate under CO2 atmosphere was also measured in presence of a selected LA-based amphiphile. The results demonstrate that the nonionic copolymers with the biodegradable and biocompatible LA-based group can significantly reduce the tension of the C vertical bar W interface. The LA-based surface active species are also capable of forming stable emulsions of water and CO2 and reducing the angle of the three-phase C vertical bar W vertical bar S contact line.