In order to predict the antioxidant activity of 22 pinoline derivatives (1,2,3,4-tetrahydro-beta-carbolines), two dimensional quantitative-structure activity relationships (2D-QSAR) analysis of 19 hexahydropiridoindoles and 12 flavonoids was realized. Five statistically significant models were obtained from randomly constituted training sets (21 compounds) and subsquently validated with the corresponding test sets (10 compounds). Antioxidant activity (pIC50) was correlated with 5 molecular descriptors calculated with the software DRAGON. The best predictive model (n = 21, q2 = 0.794, N= 2, r2 = 0.888, s = 0.157) could offer structural insights into the features conferring a strong antioxidant activity to compounds built from a pinoline scaffold prior to their synthesis.