The Thermosphere-Ionosphere-Mesosphere Electrodynamics General Circulation Model (TIME-GCM) is used to theoretically study the 6 day wave effects on the ionosphere. By introducing a 6 day perturbation with zonal wave number 1 at the model lower boundary, the TIME-GCM reasonably reproduces the 6 day wave in temperature and horizontal winds in the mesosphere and lower thermosphere region during the vernal equinox. The E region wind dynamo exhibits a prominent 6 day oscillation that is directly modulated by the 6 day wave. Meanwhile, significant local time variability (diurnal and semidiurnal) is also seen in wind dynamo as a result of altered tides due to the nonlinear interaction between the 6 day wave and migrating tides. More importantly, the perturbations in the E region neutral winds (both the 6 day oscillation and tidal-induced short-term variability) modulate the polarization electric fields, thus leading to the perturbations in vertical ion drifts and ionospheric F2 region peak electron density (NmF2). Our modeling work shows that the 6 day wave couples with the ionosphere via both the direct neutral wind modulation and the interaction with atmospheric tides.