Nanophotonics community has shown great interest in 2D materials because of their unique properties of electromagnetic field manipulation. Many of these materials exhibit strong natural anisotropy, which further opens possibilities of polarization manipulation. Here, we show that α-MoO₃, an emerging natural hyperbolic 2D material, can be combined with plasmonic nanostructures to provide strong extrinsic chirality in the visible range. A combination of biaxial anisotropy in α-MoO₃ and Fabry–Perot cavities with nanoscale features leads to different absorption of left and right circularly polarized photons, hence exhibiting circular dichroism (CD). Our simulation results predict that multilayer nanoscale-thick films including α-MoO₃ are potential candidates for achieving extrinsic chirality across the visible range. Furthermore, we show a significant CD increase when the α-MoO₃ layer is coupled with plasmonic nanohole arrays or plasmonic nanocubes. Such designs are achiral in geometry and therefore easier to fabricate. Moreover, we optimize the CD dissymmetry factor g_CD for the nanocube-based design at 780 nm, obtaining 84%. We believe that utilizing biaxially anisotropic α-MoO₃ films to control and engineer chiro-optical properties in the visible frequency range will open research directions and enable enhanced functionalities in chiro-optical control at the nanoscale, further leading to applications in chiral sensing and CD.