The aim of this study is to investigate numerically the interaction between a dispersed phase composed of micro-bubbles and a turbulent boundary layer flow. We use the Euler–Lagrange approach based on Direct Numerical Simulation of the continuous phase flow equations and a Lagrangian tracking for the dispersed phase. The Synthetic Eddy Method (SEM) is used to generate the inlet boundary condition for the simulation of the turbulent boundary layer. Each bubble trajectory is calculated by integrating the force balance equation accounting for buoyancy, drag, added-mass, pressure gradient, and the lift forces. The numerical method accounts for the feedback effect of the dispersed bubbles on the carrying flow. Our approach is based on local volume average of the two-phase Navier–Stokes equations. Local and temporal variations of the bubble concentration and momentum source terms are accounted for in mass and momentum balance equations. To study the mechanisms implied in the modulation of the turbulent wall structures by the dispersed phase, we first consider simulations of the minimal flow unit laden with bubbles. We observe that the bubble effect in both mass and momentum equations plays a leading role in the modification of the flow structures in the near wall layer, which in return generates a significant increase of bubble volume fraction near the wall. Based on these findings, we discussed the influence of bubble injection methods on the modulation of the wall shear stress of a turbulent boundary layer on a flat plate. Even for a relatively small bubble volume fraction injected in the near wall region, we observed a modulation in the flow dynamics as well as a reduction of the skin friction.