The present study explores the utility of Quantitative Structure Activity Relationship (QSAR), in- silico ADME studies and Quantitative Structure Toxicity Relationship (QSTR) for the established 2indolinone Lamotrigine Schiff base derivatives. Here, we developed 2D QSAR models for (n=6) 2indolinone Lamotrigine Schiff base derivatives as cytotoxic agents using the CTC50  values of these compounds obtained by using MTT and SRB bioassay procedure for HEp-2 and DLA cell lines. Multiple regression equations developed using the calculated physicochemical parameters showed that for HEp-2 cell lines, SRB bioassay procedure gave a better correlation between Van der Waals energy, shape flexibility index, surface area and anti-cancer activity (r2>0.95). Similarly for DLA cell lines, MTT bioassay gave better correlation between HOMO (Highest Occupied Molecular Orbital), LogP, molecular refractivity and anti-cancer activity (r2>0.99). Also, the in-silico ADME and QSTR evaluation showed that structural features of 5a compound had better pharmacokinetic and toxicity profile.