Fungicides are commonly used to prevent and treat grape (Vitis viniferaL.) diseases; however, they are potentially toxic to humans. Herein, we show that the application of S-adenosyl-l-methionine (SAM) accelerated the metabolism of various fungicides in Cabernet Sauvignon berries. The substances and enzymes involved in the metabolism of fungicides were analyzed to elucidate the effects of SAM. Results showed that SAM improved the production rate of superoxide anion, the hydrogen peroxide content, and the activities of superoxide dismutase, catalase, and peroxidase in azoxystrobin-treated berries. Additionally, SAM had a positive effect on the content of reduced glutathione and on the activities of glutathione S-transferase, glutathione reductase, and glutathione peroxidase. Importantly, the stimulatory effect of SAM on fungicide metabolism was also observed for metalaxyl and thiophanate-methyl. These results suggest that SAM can be used to improve food safety.