The α,β-unsaturated ketones known as benzalacetones are an interesting class of compounds frequently used as key intermediates in organic synthesis. Due to their conjugated system, benzalacetone and derivatives have been described as radical scavengers with potential antioxidant properties. We report here a simple and direct method to prepare functionalized α,β-unsaturated ketones via a microwaves activated Claisen-Schmidt reaction. The experimental protocol developed selectively produces benzalacetones without self-condensation product in very short reaction times and good yields. Interested in the biological properties of benzalacetones, we also studied the antioxidant potential of these compounds using an in silico study based on the DPPH• radical scavenging ability. The built mathematical model was based on the 0-3D DRAGON molecular descriptors and the artificial neural networks technique showing a correlation coefficient for the training set (R²) = 0.71, an external correlation coefficient (Q²_ext) = 0.65 . Unfortunately, the results obtained in the in-silico study revealed that synthesized benzalacetones have no antioxidant activity. The predicted results have been confirmed experimentally by an in vitro assay of DPPH• scavenging capacity.