The aim of this work is to investigate the design parameters and optimize the section profile of mechanical vane-type VGs in a sample serpentine air inlet duct by a validated computational model. The design parameters are the height, length, angle of attack and axial location of vortex generators. Total pressure loss (PLC), distortion coefficients (DC(60) and ΔPC/P) and swirl parameters (SC(60) and SI) are assessed in the duct aerodynamic interface plane (AIP) by using twelve layouts of straight vane-type VGs. The geometrical sensitivity analysis of the duct with straight VGs is performed by discrete adjoint formulation. The results of sensitivity analysis indicate that the critical regions of geometry are the leading and trailing edges of VG vanes. By changing straight profile into S-shape type, new VGs are investigated in eight layouts by applying the aforementioned parameters. S-type VGs improve the flow control performance in comparison with the straight ones. The optimal design points are chosen by two different methods with the goal of minimizing the flow loss metrics. Results indicate that all of the optimal design points have the S-type profile and they achieve over 70%, 40% and 20% reductions in distortion, swirl and total pressure loss coefficients at AIP plane, respectively.