Poaceae plant species, such as silver grass, are commonly used in mulching activities Japan. In contrast, local farmers have traditionally used Japanese knotweed (Fallopia japonica) mulch in the cultivation of solanaceous crops in the Nishi-Awa area of Japan, which is a Globally Important Agricultural Heritage Systems site. We have previously evaluated the positive effects of Japanese knotweed mulching on solanaceous crops, such as eggplants, tomato, and potato. In the present study, we observed that the naturally occurring diseases in the solanaceous crops tended to decrease when the knotweed mulching system was adopted, in comparison to when Poaceae mulch was adopted. In eggplants, leaf mold and powdery mildew decreased under Japanese knotweed mulching. We further evaluated the effects of Japanese knotweed mulching by inoculating test plants with Pseudomonas cichorii. We observed suppression of bacterial disease and tomato mosaic virus under Japanese knotweed mulching and following spraying with Japanese knotweed extracts. In addition, disease-resistance genes were expressed at high levels in Arabidopsis thaliana, a model plant, following treatment with Japanese knotweed extracts. The results suggest that Japanese knotweed has potential applications in future sustainable agriculture activities.