This study numerically explores the influence of thixotropy on flow and mixing in a staggered-herringbone micromixer (SHM), employing a structure-kinetics model to simulate the microstructure formation and breakup in thixotropic fluids. This study represents the first of its kind to incorporate a thixotropic fluid model into microfluidic mixing in channels with patterned grooves. Specifically, we examine the effects of the destruction factor ( k d ) and the thixotropy number (Th) on microstructure, flow, and mixing in the SHM, covering extensive ranges (0.01 ≤ k d ≤ 10 and 0.01 ≤ Th ≤ 100). Higher values of k d and Th , particularly for k d > 1 and Th > 1 , lead to larger spatial variations of the structure parameter (λ) and viscosity (η), with a notable decrease in λ near the groove tops, leading to the lowest viscosity in these areas. Conversely, at the groove bottoms, where shear deformation is minimal, there is less reduction in λ , leading to increased viscosity and higher flow resistance. The viscosity variations inside the grooves impede lateral flows, adversely affecting mixing in the higher k d and Th regimes. Therefore, an in-depth understanding of the complex thixotropic behaviors, as influenced by k d and Th near the grooves, is essential for achieving effective mixing in the SHM when using thixotropic fluids. Our results suggest that lowering the channel height, for a given groove depth, slightly improves the mixing of thixotropic fluids. Further enhanced mixing is achieved by combining a reduced channel height with double-sided groove patterns. [ABSTRACT FROM AUTHOR]