Curcumin possesses various pharmacological properties such as antioxidation, anticancer, and anti-inflammatory, but performs unexpected physicochemical stability and bioavailability when directly incorporate it into food or medicine. In this work, we fabricated a nano-emulsion system for the delivery and protection of curcumin. A precise and theoretically understandable fabrication procedure of curcumin-loaded nano-emulsion was proposed via systematically evaluating the effect of oil type (medium-chain triglyceride oil (MCT) and canola oil), emulsifier type (Tween-80 and lecithin), and surfactant-to-oil ratios (SOR) on the physiochemical properties and stabilities. In terms of oil phase, nano-emulsion fabricated by using MCT exhibited the highest curcumin loading capacity, smallest particle size and best storage stability. Meanwhile, Tween-80 and higher SOR were suggested to prepare monodisperse uniform, physicochemical stable and high loading nano-emulsion. In vitro digestion study indicated that most of curcumin encapsulated within nano-emulsions were released in small intestine, and the increase of particle size of the emulsions could be caused by bile salts displacing some surfactant from lipid surface. This work will finally contribute to the optimization of the curcumin nano-emulsion with better physiochemical characteristics and stability in food and beverage products.