This paper reports the investigation of a flow control strategy for an S-duct diffusers. The method incorporates stream-wise tubercles, and aims to enhance the performance of S-duct inlets by reducing the size and intensity of separated flow. These devices, bioinspired from humpback whale flippers’ leading edge protuberances, have been shown to be effective in increasing post-stall coefficients of lift of airfoils. In S-duct diffusers, the presence of convex curvature next to the separated region provides an ideal location for the installation of a tubercle-like device. The flow control effectiveness was evaluated by test-rig measurements and computational fluid dynamics (CFD) simulations of the flow in an S-duct at high subsonic flow conditions (Ma = 0.80). The S-ducts were rapid prototyped in plastic using 3D printing. Static surface pressure along the length and total pressure at the exit revealed pressure recovery, total pressure loss, swirl, and the nature of flow distortion at the S-duct exit. CFD simulations used ANSYS FLUENT with a RANS solver closed with the RKE turbulence model. The CFD simulation compared well with the test-rig data and provided useful information on flow mechanism and for understanding flow features. The performance of the baseline and variant with the flow control device was compared and flow control strategy was evaluated.