Needs for lightweight materials, reducing energy consumption, enhancing sustainability, and minimizing environmental footprint are the utmost driving factors for producing natural fibre-reinforced composites (NFRC) in the automotive sector to promote a greener future. Therefore, the present study investigates the impact of different thermoset resins, alkaline treatment (different NaOH concentrations), and fibre architecture on the mechanical behavior of sisal fibre-reinforced textile structural composite (SFRTSC) panels developed from different textile structures such as chopped fibre, unidirectional (UD), bidirectional (2D), and three-dimensional (3D) orthogonal woven structures for automotive applications. In addition, the thermogravimetric analysis (TGA) and dynamic mechanical analysis (DMA) of the SFRTSC panels were also carried out. The sisal/epoxy-based composites exhibited higher mechanical, thermogravimetric, and dynamic mechanical properties than vinyl ester and polyester-based composites. The 6 wt% NaOH treated sisal fibre-based composites showed higher mechanical properties (tensile, flexural, and impact) than 0, 2, 4, 8, and 10 wt% NaOH treated sisal fibre-based composites. Furthermore, the UD-SEC(sisal/epoxy-based composites)6 panel exhibited higher tensile, flexural, impact, and storage modulus than CH-SEC6, 2D-SEC6, and 3D-SEC6 panels. Additionally, a novel systematic mechanics-based approach was developed utilizing ABAQUS to create a mesoscale finite element model (FEM) model to evaluate the tensile and flexural response of SFRTSC.