Excessive use of plant growth stimulants and pesticides is currently a considerable problem, especially in agriculture, horticulture, and arboriculture. Understanding the impacts of these compounds and their combinations on non-target organisms is crucial to minimize unintended consequences, while maintaining their use in plant protection. The aim of this study was to test how long-term spraying with different solutions of natural biostimulator chitosan, synthetic fungicide Switch 62.5 WG, and their combinations affects the physiology of epiphytic lichen Xanthoria parietina naturally occurring in fruit orchards and farmlands. We showed that fungicides composed of fludioxionil and cypronidil, as well as the combined use of such fungicides together with chitosan, can cause the considerable impairment of lichen physiology, and these disturbances relate to both algal and fungal partners of the symbiotic association. This negative effect was especially visible in the loss of cell membrane integrity, the high level of membrane lipid peroxidation, and changes in chlorophyll fluorescence parameters on the last day of the experiment. The combined use of these agents also leads to clear disturbances in the functioning of the mitochondrial respiratory chain, which was manifested by increased NADH dehydrogenase activity, while the use of these compounds separately led to a decrease in the activity of this enzyme. We concluded that the regular use of these agents in fruit tree cultivation may cause serious ecological consequences for epiphytic lichen communities as a result of the death of lichen thalli. This study suggests that the impact of some plant protection agents, both individually and in combinations, merits further attention in terms of their impact on non-target fungi. Lichen, Chlorophyll fluorescence, Cell membrane damage, Lipid peroxidation, Dehydrogenase activity