Glucose‐induced β‐cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (K_Ca) potassium channels. Thus, ablation of the primary Kv channel of the β‐cell, Kv2.1, causes increased AP duration. However, Kv2.1^−/− islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1^−/− islets to characterize Kv and K_Ca channels and their respective roles in modulating the β‐cell AP. The remaining Kv current present in Kv2.1^−/−β‐cells is inhibited with 5 μm CP 339818. Inhibition of the remaining Kv current in Kv2.1^−/− mouse β‐cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K⁺ channels, possibly K_Ca channels, in regulating AP repolarization. Blockade of the K_Ca channel BK with slotoxin increased β‐cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased β‐cell AP amplitude by 30.6%. Interestingly, the K_Ca channel SK significantly contributes to Kv2.1^−/− mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7‐fold. Human islets also express SK3 channels and their β‐cell AP frequency is significantly accelerated by 4.8‐fold with apamin. These results uncover important repolarizing roles for both Kv and K_Ca channels and identify distinct roles for SK channel activity in regulating calcium‐ versus sodium‐dependent AP firing.