Mouse pancreatic β‐ and α‐cells are equipped with voltage‐gated Na⁺ currents that inactivate over widely different membrane potentials (half‐maximal inactivation (V_0.5) at −100 mV and −50 mV in β‐ and α‐cells, respectively). Single‐cell PCR analyses show that both α‐ and β‐cells have Na_v1.3 (Scn3) and Na_v1.7 (Scn9a) α subunits, but their relative proportions differ: β‐cells principally express Na_v1.7 and α‐cells Na_v1.3. In α‐cells, genetically ablating Scn3a reduces the Na⁺ current by 80%. In β‐cells, knockout of Scn9a lowers the Na⁺ current by >85%, unveiling a small Scn3a‐dependent component. Glucagon and insulin secretion are inhibited in Scn3a^−/− islets but unaffected in Scn9a‐deficient islets. Thus, Na_v1.3 is the functionally important Na⁺ channel α subunit in both α‐ and β‐cells because Na_v1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Na_v1.7 sequence in brain and islets is identical and yet the V_0.5 for inactivation is >30 mV more negative in β‐cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation.