FK506, also referred to as tacrolimus, is really a clinically important immunosuppressant drug and it has promising therapeutic potentials because of its antifungal, neuroprotective, and neuroregenerative activities. To create various FK506 derivatives, the dwelling of FK506 continues to be modified by chemical methods or biosynthetic path engineering. Herein, we describe the mode from the antifungal action of FK506 and also the structure-activity relationship of FK506 derivatives poor immunosuppressive and antifungal activities. Additionally, we discuss the neurotrophic mechanism of FK506 recognized to date, combined with the neurotrophic FK506 derivatives with considerably reduced immunosuppressive activity. This review suggests the chance to create novel FK506 derivatives as antifungal in addition to neuroregenerative/neuroprotective agents.