Fungi and microbes can remarkably degrade the appearance and durability of organic materials, such as wood. The inhibitory effects of natural phenolics may offer more sustainable alternatives to preserve wood than the toxic biocides that are currently used. Although pure caffeine has been proven to have antibacterial properties, the applicability of spent coffee in wood preservation has not been determined. This work conducted in vitro tests with three brown rot and one white rot fungi and demonstrated the potential of spent coffee-derived cinnamates, analyzed with high-performance liquid chromatography, as antimicrobial agents. Spent coffee at concentrations of 1% and above in the growing media caused significant growth suppression of all of the fungi. This was not only because of the caffeine, but also the other chemicals present in the residue extracts, which demonstrated that spent coffee could be used as a source of green chemicals in wood preservative formulations.