Abstract Objectives The objective of this study was to improve the water solubility and solubility of glaucocalyxin A (GLA) by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD). Methods The formation of its 1 : 1 complex with SBE-β-CD in solution was confirmed by phase-solution and spectral-shift studies. The interaction of GLA and SBE-β-CD was examined by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and ultraviolet-visible spectroscopy to determine the formation of the GLA–SBE-β-CD inclusion complex. Key findings The solubilities of GLA and its complexes were 2.38 × 102 and 1.82 × 104 μg/ml, respectively, and the values of the inclusion complexes were significantly improved by 76-fold compared with the solubility of free GLA. Moreover, a higher area under the curve0–∞ after inclusion technique was observed in the pharmacokinetics study. Conclusions The aforementioned results indicate that GLA–SBE-β-CD could be useful with a better solubility and sustained function in drug delivery.