The effect of native cow's whey and whey proteins α-lactalbumin, β-lactoglobulin, and lactoferrin was studied under the plastic house conditions for controlling the cucumber powdery mildew disease caused by Sphaerotheca fuliginea (Schlecht.) Pollaci, prophylactically and curatively sprays application during 2019 and 2020 growing seasons with improvement the total cucumber product (yield/plant). Disease severity percentages, area under disease progressive curve (AUDPC), final disease severity, efficacy percentage, microscopic observations, growth parameters, yield components and enzyme activities were investigated. Obtained results of prophylactically application indicated that the disease severity was decreased significantly (P ≤ 0.05) by the application of whey 40% dilution which scored 10 and 6%, followed by a mixture of β-lactoglobulin + α-lactalbumin + lactoferrin (10.4 and 6.4%), and lactoferrin (20.3 and 16.4%), compared to Topas 100 (9.3 and 4.3%) and control treatment (62.3 and 59.1%) during 2019 and 2020 growing seasons respectively. Furthermore, disease severity percentages were higher through curatively application than prophylactically. Consequently, the final disease severity, AUDPC values were decreased, while efficacy percentage, growth parameters, yield components and enzyme activities were increased during the experiment period with the selected treatments either under prophylactically or curatively application during the two successive growing seasons. Photography of light and scanning electron microscopy showed that the selected treatments affected the fungal hyphae, conidiophores and conidia at 24 hr after the application of selected treatments