Brown leaf spot of mulberry is caused by necrotrophic pathogen Myrothecium roridum (ascomycete) and results in the foliage loss (12-15%) during June-September in West Bengal. The management practice for brown leaf spot (BLS) includes application of dithio-carbamate fungicides; which are combative for user-health and the environment. The current study evaluates application of synthetic antimicrobial peptides (AMPs) as an alternative for BLS suppression. Eight AMPs (cecropin-mellitin derivatives) were screened initially for anti-M. roridum activity in vitro (0-72hrs at 24h interval). Four AMPs (<50μM) inhibited significant conidial growth suppression and the minimum inhibitory concentration (MIC50) recorded for most effective AMP (PRE-2) was ~23μM after 24h. LDH (lactate dehydrogenase) activity of Bombyx mori haemocytes treated with PRE-2 (50 to 175μM showed negligible cytotoxicity post-4h treatment: 0.68% at 50μM and 9.4% at 175μM. The effectiveness of PRE-2 (100μM) was assessed by spraying on BLS inflicted mulberry leaves ex vivo. Around 42% BLS suppression was recorded 20 days posttreatment. DNA isolated from PRE-2 treated and untreated samples infected with BLS were profiled with 7 SSRS and 5 ITS primers. ITS 1&4 and ITS 3&4 primer pairs revealed significant variation in band intensities between control and AMP treated samples.