<p>Vitamin B12 (cyanocobalamin) deficiency is a prevalent global health issue which has been historically treated with oral supplements or intramuscular injections. In case of pernicious anemia, there is poor absorption of Vitamin B12 in the intestine, so injection is a typical treatment option. However, injections are painful and require a trained medical professional, which can often lead to the patient visiting clinics, thereby leading to patient non-compliance. In order to overcome these disadvantages, this research investigates an alternative, minimally invasive, and patient-friendly self-administration option, transdermal delivery via dissolvable microneedle (MN) patch. We fabricate a poly (methyl vinyl ether/maleic acid) (PMVE/MA) based MN patch, a biocompatible material, for the rapid delivery of cyanocobalamin. An in-house developed polydimethylsiloxane (PDMS) mold was used to prepare the MN patch. The MN patches were characterized by optical microscopy and scanning electron microscopy (SEM) to determine MN dimensions and morphology. Mechanical strength and skin penetration ability of the MNs were assessed through a universal testing machine (UTM) and a parafilm layer model. The findings suggest that 20% PMVE/MA formulation offered sufficient mechanical strength for skin penetration and more than 90% insertion efficiency which is total number of holes created by all the MNs. Dissolution of the needles was achieved within 45 s in agarose phantom and within 120 s in porcine skin. In vitro Franz diffusion experiments revealed continuous release, achieving a cumulative release mass of ~ 229 µg of vitamin B12 within 210 min. UV–Vis and FTIR analysis confirmed excellent B12 stability in the MN patch up to 60 days. The reported observations emphasize the advantages and the translational potential of PMVE/MA-based dissolvable MN patch as a safe, effective, and user-friendly system for the transdermal delivery of vitamin B12.</p> Graphical abstract <p></p>