Summary: Microbiomes in the built environment is an emerging topic of high-relevance, as biodeterioration and biodegradation of porous and polymer materials may be major public health risk factors. Epidemiological studies have confirmed indoor airborne microorganisms and their metabolites cause significant toxic immune reactions, with clinical effects associated with more than 60% of occupants’ chronic infections. The present study reports the potential inhibitory effect on microbial and fungal colonization of hydrothermal hot-compression for the manufacture of a series of novel cellulose-based panels engineered for insulating building applications. This method was examined as it is a green manufacturing technique which simultaneously self-bonds the cellulose fibres, as well as potentially having an anti-microbial effect. The technique renders the novel materials non-toxic, additive-free, biodegradation resistant, as well as increasing the recyclability potential of the materials at their end-of-life. Prototypes were formulated from three cellulosic materials sourced from complex post-consumer coffee industry heterogeneous waste stream ─jute textile, paper cups, and coffee grounds─ holding initially high-levels of microbiological contamination. The raw materials were characterized with Infrared Spectroscopy (FTIR) and Scanning Electronic Microscopy (SEM). Microbial species were identified using culture-dependent and culture-independent DNA quantitative methods for the raw materials, as well as the processed panels. The experimental results confirmed a high-level of bacterial and fungal contamination with ubiquitous environmental bacteria such as , and , species for the Jute textile and Paper cup fibres. However, the microbes were minimized or non-detectable for all three processed panel samples. This promising result demonstrates that complex cellulosic waste materials can be converted to low-microbial biomass potential industrial feedstock for the green manufacturing of building materials.