Microbial agents such as the Bacillus species are recognized for their role as biocontrol agents against various phytopathogens through the production of diverse bioactive compounds. This study evaluates the effectiveness of Bacillus subtilis PE7 in inhibiting the growth of Didymella bryoniae, the pathogen responsible for gummy stem blight (GSB) in cucurbits. Dual culture assays demonstrate significant antifungal activity of strain PE7 against D. bryoniae. Volatile organic compounds (VOCs) produced by strain PE7 effectively impede mycelial formation in D. bryoniae, resulting in a high inhibition rate. Light microscopy revealed that D. bryoniae hyphae exposed to VOCs exhibited abnormal morphology, including swelling and excessive branching. Supplementing a potato dextrose agar (PDA) medium with a 30% B. subtilis PE7 culture filtrate significantly decreased mycelial growth. Moreover, combining a 30% culture filtrate with half the recommended concentration of a chemical fungicide yielded a more potent antifungal effect than using the full fungicide concentration alone, inducing dense mycelial formation and irregular hyphal morphology in D. bryoniae. Strain PE7 was highly resilient and was able to survive in fungicide solutions. Additionally, B. subtilis PE7 enhanced the nutrient content, growth, and development of melon plants while mitigating the severity of GSB compared to fungicide and fertilizer treatments. These findings highlight B. subtilis PE7 as a promising biocontrol candidate for integrated disease management in crop production.