The insecticidal activity of a series of 62 plant derivedmolecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure–Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculatedwith Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave- One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides.