Using the gauge-gravity duality, we study the holographic Schwinger effect by performing the potential analysis on the confining D3- and D4-brane background with D-instantons then evaluate the pair production/decay rate by taking account into a fundamental string and a single flavor brane respectively. The two confining backgrounds with D-instantons are obtained from the black D(-1)-D3 and D0-D4 solution with a double Wick rotation. The total potential and pair production/decay rate in the Schwinger effect are calculated numerically by examining the NG action of a fundamental string and the DBI action of a single flavor brane all in the presence of an electric field. In both backgrounds our numerical calculation agrees with the critical electric field evaluated from the DBI action and shows the potential barrier is increased by the presence of the D-instantons, thus the production/decay rate is suppressed by the D-instantons. Our interpretation is that particles in the dual field theory could acquire an effective mass through the Chern-Simons interaction or the theta term due to the presence of D-instantons so that the pair production/decay rate in Schwinger effect is suppressed since it behaves as $e^{-m^{2}}$. Our conclusion is in agreement with the previous results obtained in the deconfined D(-1)-D3 background at zero temperature limit and from the approach of the flavor brane in the D0-D4 background. In this sense, this work may be also remarkable to study the phase transition in Maxwell-Chern-Simons theory and observable effects by the theta angle in QCD.