In this numerical study, a new type of serpentine micromixer involving mixing units with a non-rectangular cross-section is investigated. Similar to other serpentine/spiral shaped micromixers, the design exploits the formation of transversal vortices (Dean flows) in pressure-driven systems, associated with the centrifugal forces experienced by the fluid as it is confined to move along curved geometries. In contrast with other previous designs, though, the use of non-rectangular cross-sections that change orientation between mixing units is exploited to control the center of rotation of the transversal flows formed. The associated extensional flows that thus develop between the mixing segments complement the existent rotational flows, leading to a more complex fluid motion. The fluid flow characteristics and associated mixing are determined numerically from computational solutions to Navier–Stokes equations and the concentration-diffusion equation. It is found that the performance of the investigated mixers exceeds that of simple serpentine channels with a more consistent behavior at low and high Reynolds numbers. An analysis of the mixing quality using an entropic mixing index indicates that maximum mixing can be achieved at Reynolds numbers as small as 20 in less than four serpentine mixing units.