["Archives of Insect Biochemistry and Physiology, Volume 122, Issue 4, August 2026. ", "Optimized extracts from Ficus carica pruning waste exhibit strong biological activity against major stink bug pests. Complementary in silico analyses suggest this efficacy relies on pest‐specific acetylcholinesterase inhibition, predicting a promising, pollinator‐safe alternative for sustainable agriculture.\n\n\n\n\n\nABSTRACT\nThe Neotropical stink bugs Euschistus heros and Diceraeus melacanthus are major pests of soybean and maize in South America, yet current chemical control strategies face widespread resistance, highlighting the urgent need for sustainable alternatives. This study investigates Ficus carica pruning residues as a source of selective botanical insecticides, integrating optimized extraction, phytochemical profiling, bioassays, and molecular modeling. Eight extracts were prepared under varying solvent, temperature, and acidity conditions, and analyzed for total phenolic content (TPC) and the key furanocoumarins psoralen and bergapten. Acidification enhanced overall mass yields, while mild ethanol extraction at room temperature selectively maximized furanocoumarin recovery, yielding psoralen concentrations up to 14.83 mg g−1, which is substantially higher than previously reported in leaves or fruit. Biological evaluation of the optimized ethanolic extract (ERA) revealed strong insecticidal activity, with 86% mortality of E. heros and 40% of D. melacanthus nymphs at 48 h, and a calculated LC50 of 1232 mg L−1 for E. heros. The differential susceptibility between species suggests both metabolic and cuticular factors influence efficacy. Computational docking and phylogenetic analyses suggested a potential mechanistic basis for the observed selectivity: furanocoumarins are predicted to bind hemipteran AChE via a compensatory polar scaffold, whereas binding to Apis mellifera AChE is predicted to be weaker due to lineage‐specific differences in aromatic density within the catalytic gorge, potentially explaining the minimal off‐target susceptibility. The molecular modeling results characterize these compounds as low‐affinity, reversible inhibitors, combining effective pest control with a favorable safety profile for pollinators. The present work demonstrates that valorizing agro‐industrial waste from F. carica can yield potent, selective, and environmentally safer insecticidal agents. The integration of extraction optimization, biological evaluation, and molecular modeling provides a robust framework for developing sustainable botanical insecticides, advancing circular economy principles in pest management and offering promising alternatives to synthetic neurotoxins."]