A Good's buffer ionic liquid (GB-IL) composed of quaternary ammonium cations and Good's buffer anions is first introduced into a microemulsion system as a self-buffering and biocompatible electrolyte. The effects of the constituting ions of a GB-IL and their concentrations on the phase behavior of the anionic surfactant SDBS stabilized n-octane–H₂O microemulsion system were studied for the first time using the ε–β fish-like phase diagram method. The result indicates that the phase behavior of the above microemulsion system is greatly affected by GB-IL cations with a longer alkyl chain on the cation being more favorable for phase inversion. Compared with NaCl, a GB-IL of the same concentration is more efficient for achieving phase inversion, due to the dual role of an electrolyte and a co-alcohol. In addition to the phase behavior, the stability of horseradish peroxidase (HRP) solubilized in an SDBS stabilized bicontinuous microemulsion is also affected by a GB-IL. It is found that the variation of the cationic alkyl chain has a negligible effect on the microemulsion microstructure, but has a significant influence on the stability of the solubilized HRP. At a fixed concentration of the GB-IL, the quaternary ammonium cation with a longer alkyl chain is better for the stabilization of the HRP activity. For a given GB-IL, a higher level of the GB-IL results in a better HRP stability. More importantly, the GB-IL-buffered microemulsion, at the same level of the buffering salt, is more advantageous than the phosphate-buffered one for the stabilization of the HRP activity. This advantage is more pronounced for higher concentrations of the GB-IL. This difference in the HRP stability, caused by the buffering salts, should be ascribed to the microemulsion microstructure effect as well as the Hofmeister effect. The present study provides a guideline for the construction of a bicontinuous microemulsion with a simplified composition and stabilizing effect on the solubilized enzyme.