Cellulose diacetate (CDA) is a biodegradable biobased polymer, which is not easily melt-processable with a narrow window between flowing and decomposition temperature. Selecting the appropriate plasticizer and evaluating its effect on the properties are important for the application developments of CDA materials. In this paper, eco-friendly plasticizers, such as glycerin (GL), diacetin (DA), triacetin (TA) and polyethylene glycol (PEG) are necessarily introduced. The plasticizing effect is evaluated by harmonic interface energy between CDA and plasticizer from contact angle test. Compared with solubility parameter method, the interfacial method is more effective to estimate PEG with different molecular weight in CDA. Thermal behaviors verify the interfacial method works. Lower interface energy of CDA-DA shows lower glass transition temperature (Tg) determined by differential scanning calorimetry (DSC). Meanwhile, mechanical property, transparency and moisture permeability are all related to the interfacial effects of plasticizers. For instance, the elongation at break of CDA-DA and CDA-TA, which have lower interfacial energy, increase from 14% to 26% and 29%. The CDA-DA and CDA-TA films also have high visible light transmittance about 90%. The moisture permeability of plasticized CDA film increases with the decreased interface energy between water and plasticizer. Interfacial method provides a new route for preparing high-performance CDA materials.