Control methods have faced challenges in effectively managing the spread and damage caused by the fall armyworm (FAW), Spodoptera frugiperda, across various crops worldwide, highlighting the need for more sustainable and integrated approaches. This study explored the insecticidal effect of the essential oil (EO) of lavender (LV) (Lavandula multifida L.), cyantraniliprole (CY), and emamectin benzoate (EM) insecticides on FAW larvae. Toxicity, biological, and biochemical assays were employed to elucidate the impact of the two insecticides individually or combined with LV EO. Additionally, in silico molecular docking investigations were performed for eucalyptol (the major component of LV EO) and for CY against the acetylcholine esterase (AChE) enzyme (PDB ID: 6xyu) and cytochrome P450 (PDB ID: 2q6n). EM was the most toxic compound to FAW larvae with an LC50 of 0.0073 mg L−1, followed by CY and LV EO. The chi-square (χ2) test confirmed the synergistic effect of the LV EO/CY combination and the antagonistic effect LV EO/EM combination on FAW larvae. Biological development studies revealed that both LV EO/CY and LV EO/EM combinations impacted the larval and pupal durations. The biochemical assays indicated that the P450-specific activity was activated by LV EO (at LC25), CY (at LC25 & LC50), and their binary combination (at LC25:LC25). In addition, the LV EO/CY combination significantly activated the AChE and GST-specific activity, and the LV EO/CY combination and CY (at LC50) significantly activated α-esterase- specific activity. Molecular docking investigations revealed energy scores (S) of −6.7729 and −7.7644 kcal/mol for eucalyptol and CY, compared to −7.0993 kcal/mol for PDB ID: 6xyu ligand. The current results can serve as baseline data for utilizing the LV EO/CY combination in the integrated pest management (IPM) of FAW.
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