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This study aimed to select proper lipids for designing astaxanthin-loaded nanostructured lipid carriers (astaxanthin-NLC), and then to evaluate the influence of formulation composition on astaxanthin-NLC characteristics and optimize the formulation by response surface methodology. Tween 80 and lecithin were employed as emulsifier, and oleic acid and glyceryl behenate were selected as appropriate lipids. Astaxanthin-NLC (with 5% lipid phase) were prepared by melt emulsification–sonication technique and stored at ≈ 19 °C for 25 days. The lipid phase to Tween 80 ratio (LTR) and oleic acid content of the lipid mixture (OCL), as independent variables, had significant effects on physical characteristics of fresh formulations and their storage stability. The optimum formulation of astaxanthin-NLC (with OCL: 22.4% and LTR: 1.8) had greater values of particle size, polydispersity index and ζ-potential than the …