Renewable bio-based materials are gaining traction as innovative solutions in the construction industry, aimed at minimizing material waste, reducing the extraction of non-renewable resources, and lowering the carbon footprint. This study showcases an innovative combination of bio-based insulation, structural components, and façade materials in three bio-based wall panels, highlighting the potential of integrating diverse bio-based materials to enhance sustainability and circularity in construction, whilst providing high hygrothermal performances. The first panel, a ‘circular bio-based’ wall, was designed following principles of circular economy, using sheep wool insulation, clay board, and bio-plastic cladding. The panel was tested at the Building Research Park (BRP) at the University of Bath to investigate the panel’s thermal and hygric properties in a dynamic environment. The second and third bio-based panel are circular reclaimed timber frames combined with innovative bio-based elements such as mycelium and cellulose-textile insulation. The two panels are currently under development. However, they were simulated using WUFI Pro to recreate the same environmental condition of the ‘circular bio-based’ panel. Results from the experimental testing indicated a U-value of 0.14 W/m2K or lower for the first panel. Some interstitial condensation occurred and limited moisture buffering properties were observed (35 g/m2). The second and third panel showed a U-value of 0.24 W/m2K and 0.22 W/m2K facing North, respectively. No condensation was found and some negligible moisture buffering properties were observed. The tests conducted offered a comprehensive understanding of the prototypes’ strengths and weaknesses, enabling significant design improvements that will accelerate their adoption within the construction sector.