Luffa cylindrica M. Roem, is commonly called sponge gourd or Egyptian cucumber. In September 2018, several plants showing symptoms of powdery mildew were observed in some fields at different locations in Egypt. Identification and pathogenicity tests indicated that the causal fungus of powdery mildew disease of luffa cylindrica was Podosphaera xanthii. Results of surveyed luffa plants grown at different field localities of northern Egypt, for powdery mildew disease incidence revealed that the maximum record (57.33%) of disease occurrence was recorded in some fields belonging to Beheira governorate followed by, Alexandria and Sharqia (53.67% and 48.00%, respectively). Meanwhile, fewer occurrences were observed in Kafer El-Sheekh governorate (45.33%). We applied biocontrol agents as a foliar spray against powdery mildew in vitro and under field conditions. The effects of some essential oils, organic acid and bioproducts were also studied. All treatments significantly reduced P. xanthii compared to untreated plants. Chaetomium globosum and Saccharomyces cerevisiae alone or grown on rice straw and/or bagas showed highly reduced disease incidence compared to the other treatment. From the present study it could be suggested that the usage of biocontrol formulated on rice straw might be used as an easily applied, safe and cost effective control method against powdery mildew diseases.