Iontronic devices or “ion pumps” enable electronically controlled delivery or of molecules through ion–selective membranes with exceptional spatiotemporal resolution. This transport occurs without any fluid movement or mechanical components, making it particularly well suited for precise and reliable therapeutic release. However, this transport mechanism is inherently limited to charged, low molecular weight (<500 g/mol) and electrochemically stable compounds. To overcome these constraints, we present BioSWITCH, a hybrid delivery strategy that decouples molecular transport from therapeutic activation by integrating iontronic delivery with bioorthogonal click–to–release (C2R) chemistry. In this system, charged aminoethyl tetrazines are delivered iontronically to a localized prodrug reservoir, where they undergo an inverse electron demand Diels-Alder (IEDDA) reaction with trans–cyclooctene (cTCO) caged compounds. This enables precise, bioorthogonal activation of therapeutic payloads, irrespective of their molecular size or charge. We demonstrated programmable tetrazine delivery over multiple days using periodic device operation and subsequently validated the concept through activation of potent anti mitotic agent Combretastatin A-4 (CA4). Iontronic tetrazine delivery activated the bound CA4-prodrug, resulting in antiproliferative effects in glioblastoma cell models. Building on these results, we also achieved controlled release of the protein bovine serum albumin (BSA), demonstrating the platform’s ability to overcome the size limitations of conventional iontronic systems. The amount of released protein scaled linearly with the duration of tetrazine delivery, enabling precise, time dependent control over macromolecular release. Together, these results establish BioSWITCH as a novel approach that extends the capabilities of iontronic pumps toward the controlled release of both small molecules and macromolecular therapeutics.