A transdermal patch that combines microneedle array (MA) with iontophoresis can achieve synergistic and remarkable enhancement of drug delivery with precise electronic control. However, the development of an MA patch combined with iontophoresis that can enable in situ treatment, easy self-administration, and controllable delivery of liquid macromolecular drugs is still a challenge. Here, we presented an iontophoresis-driven porous MA patch (IDPMAP) for in situ, patient-friendly, and active delivery of charged macromolecular drugs. IDPMAP integrates porous MA with iontophoresis into a single transdermal patch, thus realizing the one-step drug administration strategy of "Penetration, Diffusion, and Iontophoresis." Moreover, a matching portable iontophoresis-driven device was developed for drug self-administration of IDPMAP. In vitro and in vivo studies showed that IDPMAP had approximately 99% skin penetration rate, negligible cytotoxicity, and good biocompatibility without skin irritation and hypersensitivity. In vivo transdermal delivery of insulin in type 1 diabetic rats demonstrated that IDPMAP could effectively deliver insulin nanovesicles and produce a robust hypoglycemic effect on the rats (maintain normal blood glucose for approximately 5.4 h), with more advanced controllability and efficiency than that achieved by pristine MA or iontophoresis. IDPMAP and its portable iontophoresis-driven device are user-friendly and thus show a promising potential for drug self-administration at home.