The fungal degradation of the complex polymeric systems based on poly(lactic acid) (PLA) and natural bioactive compounds (chitosan and powdered rosemary alcoholic extract) was studied. Two fungal strains, Chaetomium globosum and Phanerochaete chrysosporium were tested. Both fungi characteristics and changes in morphology, structure and thermal properties were monitored. Biochemical parameters as superoxide dismutase, catalase, soluble protein and malondialdehyde have been determined at different time periods of fungal degradation. The fungi extracellular enzyme activities are slightly decreased in the case of composites containing bioactive compounds. The presence of natural compounds in the PLA-based polymeric system determines an acceleration of fungal degradation and probably the chemical hydrolysis, which further helps the attachment of fungi on the surface of polymeric samples. Significant decreases in average molecular mass of the polymeric samples were observed by fungi action; accompanied by structural changes, increase in crystallinity and decrease of thermal properties and the loss of the physical integrity and finally to degradation and integration of fungal degradation products into environmental medium. It was found that both fungi tested are efficient for PLA-based materials degradation, the most active from them being Chaetomium globosum fungus.