Due to relatively wide range of hues and great biocompatibility, natural dyes are now frequently employed in replacing synthetic dyes in many areas with high safety requirements. Natural dyes, however, are often ruined or faded in the process of storage and application because of their unique chemical structure. In this paper, packaging ink microcapsules with high stability and biocompatibility was prepared by in situ polymerization with polymethyl methacrylate (PMMA) as wall material, and gardenia blue (GB) natural dye as core material. The effects of the preparation parameters, such as dosages of the core material, emulsifier, and initiator on the morphology, structure, and stability of GB-PMMA microcapsules were characterized by means of scanner electron microscopy (SEM), fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The results showed that the encapsulation efficiency of GB-PMMA microcapsules can reach up to 84.8%. GB-PMMA microcapsules exhibit smooth and dense spherical appearance. Thermal stability of natural dye GB was improved by nearly 40% after being microencapsulated. Moreover, the adhesion and acid/alkali resistance grade of packaging ink containing GB-PMMA microcapsules are all higher than or equal to 3 level. Therefore, the GB-PMMA microcapsule samples prepared in this paper is expected to be used for printing ink of food packaging owing to their high stability and biocompatibility. Display omitted