Abstract. Life-Cycle Assessment (LCA) stands as a vital tool in gauging the environmental impacts of building endeavors. Extending LCA to emerging research practices like advanced digital manufacturing of bio-based materials becomes pivotal for refining materials, appraising outcomes, and steering architecture toward sustainable development and circularity goals. To outline the main obstacles and to provide a potential methodology, the paper presents two cases of application of LCA to digital fabrication with bio-based materials in experimental research practice. The application is framed within the ISO and EU standards for LCA and is tested through an ex-post “cradle to construction” analysis of two ERC funded projects developed by the Center for Information Technology in Architecture (CITA) at the Royal Danish Academy. Specifically, a product LCA is performed for bio-polymeric composited 3D robotic fabrication using a novel collagen-based 3D print material, and a comparative LCA is carried out for Glulam manufacturing optimization connecting data from the timbers source in the forest and sawmill with its design and fabrication. In both cases, the prototypes assembly and exhibition are covered by the analysis. The unavailability of data, difficulties in standard protocols adaptation and material and energy flows tracing in the research process emerge as the main barriers and contribute to aggravate the analysis’s uncertainty. The paper shows how to manage such uncertainties via Sensitivity Analysis to evaluate design options according to different impact scenarios. The knowledge established and the methodology outlined in this research could be useful for researchers, designers and industry in the implementation of sustainable digital fabrication processes and new construction materials.