AbstractThe transdermal route is attractive for the minimally invasive administration of small and large molecules. Microneedles (MNs) are particularly promising because of their straightforward, cost‐effective, and safe administration. But precise control over their degradation rate within the skin remains a challenge. Here, porous silicon microneedles (pSi MNs) with controlled degradation rate, tunable porosity, high payload capacity, and mechanical stability are introduced for transdermal delivery of bioactive molecules. pSi MNs are fabricated by combining dry and wet etching methods. After creating MNs via deep reactive ion etching, a porous surface is obtained by electrochemical anodization, producing pSi MNs of about 42 µm length, tip diameter < 1 µm, and conformal porous layers. The biodegradability and the mechanical properties of pSi MNs are adjusted by changing the thickness of the porous layer from 1.5 to 4.0 µm. Both small and macromolecular drug molecules are uniformly loaded into the porous layer of the pSi MN arrays. Ex vivo penetration experiments on porcine tissue demonstrate efficient transdermal delivery using pSi MNs. The novel pSi MNs with tunable porosity, biodegradability, and mechanical strength offer opportunities for the delivery of biotherapeutics through the skin, engendering innovations in pharmaceutical sciences.