This study investigated the biodegradation behavior of cotton fabrics treated with polypyrrole, a polymer with conductive and antibacterial properties. Fabric samples were buried in compost-enriched soil for 10, 30 and 90 days. The biodegradation level was initially estimated by a visual inspection of the fibers and by the determination of the fabric weight loss. Other physical-chemical changes of fibers during the biodegradation process were analyzed by microscopy, thermal analyses and infrared spectroscopy. The surface resistivity of the fabrics was also measured. The results obtained comparing the bare cotton samples and the polypyrrole-added ones suggested that, on the one hand, polypyrrole hindered/delayed the biodegradation of cotton in compost-enriched soil, probably exercising its inherent antimicrobial feature during the first period of burial. On the other hand, over time, polypyrrole seemed to represent the first compound attacked by the microorganisms, preserving the cotton substrate. Despite the absence of dedicated literature regarding polypyrrole biodegradation, the mechanism hypothesized in this paper involves the loss of conjugation, as a consequence of de-doping, oxidized functionalities up to local cycle breaking.