Composed of a supramolecular hydrogel and a heme model compound, a new type of artificial peroxidase shows high catalytic activity in organic media. The activity of this new type of artificial enzyme is significantly higher than that of the heme model compounds alone. Changes in the distal substituents above the coordinated-metal centers of the model compounds directly modulate catalytic activity. This supramolecular-hydrogel-based artificial enzyme is most active in toluene, reaching about 90% of the nascent activity of horseradish peroxidase. Moreover, this study confirms that the incorporation of the heme models into the nanofibers of gelators accounts for most of the enhancement of catalytic activity.