AbstractAndrographolide (ADG) encapsulation was carried out on MOFs MIL‐53(Al) and ZIF‐8 by high‐pressure (0.3 GPa) contact. This methodology is not only environment‐friendly but also energy/time‐saving and gives rise to ADG‐MOFs with physical features equivalent to those of materials obtained by common liquid phase encapsulation. The loaded MOFs were characterized through TEM, SEM, XRD, TGA, FT‐IR, BET, and NMR. The observed decrease in the intensity of ADG XRD peaks is due to the adsorption of ADG into the MOFs. TGA showed the decomposition step of ADG in the range of 200–300 °C in both loaded MOFs. FT‐IR also showed intense signals of the ADG in the synthesized materials. The dissolution profile of ADG in MIL‐53(Al) in PBS (pH=7.4) was carried out showing that the drug was released up to 96 % after 75 h. Solid‐state NMR confirmed the interactions between ADG molecules and ZIF‐8 groups and the formation of a hydrogen bond between the carboxylic group of ADG and the hydroxyl group of MIL‐53(Al). Coefficient partition studies determined that both MOFs did not improve the hydrophilicity of the ADG, due to the loading of the drug preferably occurring by interactions in the hydrophobic areas within the pores of the MOFs.