Downy mildew of squash caused by Pseudoperonospora cubensis is considered one of the serious diseases that affect cucurbits crops in Egypt and all the world. This study was conducted to find alternative safe methods for controlling downy mildew disease. The use of plant extracts, essential oils, growth regulators and foliar fertilization with nitrogen, potassium and phosphorus showed that these treatments reduce disease incidence and lead to a significant increase in yield compared to untreated plants. 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. 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. Application of the disease control methods to squash plants increased chlorophyll, total sugars content and proline concentration compared to the untreated control plants.