Downy mildew of cucurbits is very important disease worldwide. This investigation was carried out in order to achieve safe control method(s) to such disease. The obtained results courld be summarized as following: Pseudoperonospora cubensis is the causal organism of downy mildew disease of either cucumber or squash and it was first recorded in Egypt on watermelon at 1935. Spraying cucumber plants with the tested plant extracts reduced both percentage of infection (P.I.) and the disease severity (D.S.) in Comparison with the untreated control treatment, significantly. Yield production was also increased significantly. Thuja plant water extract showed the best efficiency in reducing the disease incidence, followed by clove one while black cumine plant extract showed the least efficiency. The application of the plant essential oils greatly reduced downy mildew disease of cucumber and squash cultivar, and increased yield production in comparison with the untreated control plants. Clove essential oil followed by mint one gave the best results. Application of the tested growth regulators to cucumber (Madaen cv.) and Squash (Aziad cv.) plants significantly reduced the disease incidence and improved yield production, in comparison with control, both at 2018-2019 and 2019-2020 growing seasons. In this request, Cytokinin and Gibberellin showed the best efficiency, while Auxin was the least effective one. Foliage fertilization with NPK fertilizers greatly affected cucumber and squash cultivar downy mildew diseases incidence and increased yield production compared to control, significantly. However, it was noticed that increasing nitrogen doses led to the increment of both (P.I.) and (D.S.). The best yield production was obtained when the highest level of potassium was applied. Application of Cabriodio 11.2% fungicide suppressed the disease incidence, completely. In the meantime, high increment of yield production was obtained, compared to the other treatments. Growth characteristics of squash plants i.e., plant height, leaf area, root length, shoot length, plant fresh weight and plant dry weight were significantly increased in response to the application of any tested control methods compared to the untreated control plants. 10. Total water content (TWC), relative water content (RWC) and transpiration rate of squash plants were remarkably increased in response to the application of either Gibberellin, black cumin oil, clove oil (10%), mint oil (5%), Thuja extract and/or the fungicide in comparison with the untreated control. 11. Application of the disease control methods to squash plants increased chlorophyll, total sugars content and proline concentration compared to the untreated control plants. 12. Chemical analysis of N. sativa essential oil indicate that this oil mainly contained vanillic acid (89.94 mg/ml) and gallic acid (29.59 mg/ml). 13. Peppermint oil contained gallic acid (18.6 mg/ml) and caffeic acid (4.8 mg/ml). 14. Clove essential oil has high amount of eugenol (72.72 mg/ml), eugenol acetate (2.1 mg/ml), guaicol (4.16 mg/ml) and methyl quaiacol (9.79 mg/ml). 15. Thuja plant water extract contained tannic acid (38.16 mg/100 g sample) and catechin (33.54 mg/100 gm). 16. The most frequently present compounds in clove plant extract was eugenol (79.72 mg/100 g sample) and limonin (3.52 mg/100 g sample).