In an in vitro study with five clinical isolates of dermatophytes, the MIC(50) and MIC(100) values of silver nanoparticles (AgNPs) ranged from 5 to 16 and from 15 to 32 μg ml(- 1), respectively. The combined treatment of AgNPs with atmospheric pressure-air cold plasma (APACP) induced a drop in the MIC(50) and MIC100 values of AgNPs reaching 3-11 and 12-23 μg ml(- 1), respectively, according to the examined species. Epidermophyton floccosum was the most sensitive fungus to AgNPs, while Trichophyton rubrum was the most tolerant. AgNPs induced significant reduction in keratinase activity and an increase in the mycelium permeability that was greater when applied combined with plasma treatment. Scanning electron microscopy showed electroporation of the cell walls and the accumulation of AgNPs on the cell wall and inside the cells, particularly when AgNPs were combined with APACP treatment. An in vivo experiment with dermatophyte-inoculated guinea pigs indicated that the application of AgNPs combined with APACP was more efficacious in healing and suppressing disease symptoms of skin as compared with the application of AgNPs alone. The recovery from the infection reached 91.7 % in the case of Microsporum canis-inoculated guinea pigs treated with 13 μg ml(- 1) AgNPs combined with APACP treatment delivered for 2 min. The emission spectra indicated that the efficacy of APACP was mainly due to generation of NO radicals and excited nitrogen molecules. These reactive species interact and block the activity of the fungal spores in vitro and in the skin lesions of the guinea pigs. The results achieved are promising compared with fluconazole as reference antifungal drug.