Microbial-derived bioactive metabolites offer a promising strategy for sustainable plant disease management, but their efficacy against Phytophthora palmivora in durian plants and the associated host metabolic responses remain poorly understood. This study evaluated the protective effects of a crude extract from Priestia aryabhattai PTKU-123 against Ph. palmivora in durian seedlings and characterized the associated metabolic changes in durian seedling leaves. Anti-oomycete activity was evaluated in vitro, followed by greenhouse assessment of disease protection and untargeted LC–QTOF–MS metabolomic profiling of durian leaves. The crude extract at 5 mg mL⁻¹ strongly inhibited Ph. palmivora mycelial growth in vitro (95.67 ± 0.74%), with efficacy comparable to fosetyl-aluminum (99.93 ± 0.14%). Under greenhouse conditions, crude extract-treated seedlings exhibited significantly lower disease severity (26.11 ± 6.74%) than pathogen-inoculated controls (66.67 ± 6.67%) and protection comparable to fosetyl-aluminum-treated plants (23.33 ± 5.77%). Metabolomic profiling of durian leaves revealed a distinct metabolic response associated with crude extract treatment, with enrichment of inositol phosphate metabolism, nitrogen metabolism, fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and tryptophan metabolism. These findings demonstrate that the PTKU-123 crude extract suppresses Ph. palmivora disease in durian seedlings and that disease protection is accompanied by alterations in defense-associated metabolism, supporting its potential as a microbial-derived strategy for sustainable management of Phytophthora disease in durian.