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A bis-demethoxy curcumin microemulsion was successfully prepared using the method of pseudo-ternary phase diagrams combined with an orthogonal test in a 3-phase system (O phaseϭac-tive ingredient; S phaseϭsurfactants; W phaseϭwater). The best transparent region for preparing the bis-demethoxy curcumin microemulsion was formed when Termul-200 (an alkylphenol polyether block copolymer emulsifier) and sodium dodecyl benzene sulfonate (SDBS) (4 : 1 w/w) were used as surfactants (S phase), isopropanol (30% in S phase) as a co-surfactant, and a bisdemethoxy curcumin DMF solution (30%) as the active ingredient (O phase). According to the infinite dilution region of the best phase diagram, the best ratio among O, S and W phases for preparing the bis-demethoxy curcumin microemulsion was a weight ratio of 4.5 : 20 : 75.5. Stability tests showed that all the indicators of our prepared microemulsion met the storage stability criteria. Our results suggested that the combination of the pseudo-ternary phase diagram and orthogonal test analysis provided an effective approach for designing a microemulsion formulation.