Background: Curcumin is an important natural compound that has been extensively studied for its multifunctional pharmacological activities. Different nanotechnological techniques have been applied for improving its poor solubility and bioavailability. Objectives: This research aimed to study the effect of formulation variables on the entrapment efficiency of curcumin-loaded niosomes (curcusomes) made by a thin-film hydration technique. Methods: Curcumin-loaded noisome were prepared using the thin-film hydration technique using Span 40 and 60 as surfactants, in addition to bile salts and cholesterol. The surfactant and cholesterol were added to curcumin in different ratios, with/without the addition of 10% of bile salts. Results: Eighteen formulae were obtained from the addition of bile salts and spans. Results showed that increased surfactant concentration and low cholesterol ratio enhanced the %EE of formulae. Conclusion: The formulation of curcumin-loaded niosomes with the thin-film hydration method where span 40 or span 60 are used as surfactant enhances the %EE of curcusomes which in turn improves the poor solubility and bioavailability of curcumin. The addition of bile salts enhanced the %EE which will be investigated furtherly for more in vitro and in vivo studies.