Total-pressure losses and distortion in an aggressive offset diffuser, induced by secondary-flow vortices and boundary-layer separation, are mitigated using fluidic actuation for the aerodynamic interface plane Mach number up to 0.57. Although total-pressure recovery is primarily impacted by separation in each of the diffuser’s turns, distortion is governed by counter-rotating streamwise vortices that advect low-momentum fluid from the wall region into the core flow. The present investigations have shown that secondary-flow vortices couple to the outboard segments of the separated-flow domains. Therefore, fluidic control of the scale and topology of the trapped vorticity within the internally separated flow can be leveraged to control the structure and strength of the ensuing secondary vortices, and thereby significantly reduce flow distortion and losses. In the present investigations, fluidic control is effected by a spanwise array of oscillating jets that are placed just upstream of the second-turn separation domain. Actuation directly affects the local flow separation, but it also alters the spacing and diminishes the strength of the base-flow streamwise vortices by forming and adjoining streamwise-vorticity concentrations of opposite sense. Additionally, the spanwise distribution of the actuator array was optimized to reduce circumferential distortion by 60% at actuation to a diffuser mass-flow-rate ratio lower than 0.5%.