Onion (Allium cepa L.) is among the most significant vegetable crops cultivated commercially worldwide. A major challenge in onion production is downy mildew, caused by Peronospora destructor. This common leaf disease impacts both the yield of onion bulbs and the seed production in the second year. One of the key strategies to manage this disease is the application of fungicides. Six fungicides were used in this study i.e Copper oxychloride, Azoxystrobin-Difenoconazole, Cyazofamid-Cymoxanil, Mancozesb-Dimethomorph, Trifloxystrobin–Tebuconazole, and Dimethomorph-PyraclostrobinIn addition, four chemical inducers, Salicylic acid, Chitosan, Humic acid and Ascorbic acid were tested. These inducers were combined with the recommended Azoxystrobin-Difenoconazole fungicide at the rate of 1:1 individually. These fungicides and chemical inducers were evaluated for their effectiveness in reducing infection with downy mildew diseases on onion caused by Peronospora destructor under field conditions. Besides, antioxidant enzymes activities (polyphenol oxidase and peroxidase enzymes) were assessed in onion. Results showed that all the fungicides and chemical inducers signif-icantly reduced the severity of downy mildew and increased the activities of antioxidant enzymes activity (POX and PPO). Moreover, Azoxystrobin-Difenoconazole, Ascorbic acid at conc. 0.704 g, and Chitosan at concentration of 2 g combined with Difenoconazol- Azoxystrobin had the lowest disease severity and the highest efficacy. Meanwhile, Copper oxychloride, Chitosan, and the combination of Difenconazol-Azoxystrobin with Chitosan at concentration of 2 g resulted in the highest increase in polyphenol oxidase and peroxidase activities.