Curcumin is a molecule with therapeutic interest in diverse fields, particularly food science, due to having several features such as being anticancer, anti-inflammatory, anti-amyloid, anti-Alzheimer’s disease, and anticystic fibrosis. However, it is rarely used for such aims due to its poor solubility and low bioavailability. Hence, using Box-Behnken Design, an attempt was made to optimize the preparation of biocompatible curcumin-loaded niosome based on sucrose stearate as non-ionic surfactant and cholesterol. For this end, effects of independent variables, including sucrose stearate molar ratio (X 1 ), choles- terol molar ratio (X 2 ), and curcumin content (X 3 ), were investigated on niosomal mean vesicle size (Y 1 ), zeta potential (Y 2 ), polydispersity index (Y 3 ), and entrapment efficiency (Y 4 ). The optimized niosomal formulation exhibited mean particle size of 127.33 nm with the narrow size distribution of (PDI = 0.40), zeta potential (-26.45), and 99.89% of loading efficiency. The FTIR, XRD, and DSC analysis confirmed a successful encapsulation of curcumin. In addition, the Weibull model (R 2 adjusted = 0.99) was evaluated as the best model for fitting curcumin release data from sucrose stearate based niosomes. This study showed that nanoencapsulation of curcumin using sucrose stearate resulted in the production of niosomes with acceptable mean vesicle size and exceptional encapsulation efficiency. Furthermore, the entrapment stability of sucrose stearate based niosomes during one month and their slow release pattern under acidic conditions depicted their potential as a delivery system, especially in food products with long storage time.

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