Locusts are uniquely unpredictable pests with the phenotypic advantage to form large swarms that can quickly eliminate vast quantities of agricultural produce. Recent outbreaks in East Africa spread across continents to Southwest Asia, and caused massive economic losses and created food insecurity. Locusta migratoria has the largest global distribution of any acridid species, and is a major crop pest in the Eastern hemisphere. Despite this, efforts to control this pest are still highly reliant on chemical insecticides. Biocontrol for this pest species and other acridids has remained stagnant in recent years, with Metarhizium fungi being the only commercial biocontrol product against locusts. While many arachnid venoms have been tested in crickets within the order Orthoptera, there has been a lack of systematic screening against key locust pests. We therefore started a systematic large-scale screening of >100 arthropod venoms (mainly from spiders and scorpions) against locusts pests such as the giant grasshopper (Valanga irregularis) and the migratory locust (Locusta migratoria). From screening 173 venoms by injection into 1st to 2nd instar nymphs, we have isolated six venom peptides with potent activity against one or both acridid species and we are currently in the process of identifying the sequences. Any of the locust-active peptide sequences will be produced by chemical synthesis in sufficient amounts to enable their detailed characterisation in vivo against on-target locust species and off-target insects such as honeybees and Australian native bees. In addition, we’ll be examining the molecular targets of the locust-active synthetic peptides using patch-clamp electrophysiology on locust dorsal unpaired median neurons. Oral toxicity assays will then be used for the synthetic lead peptides to obtain insights into potential application strategies for subsequent field trials.