Therapeutic secondary metabolites have gained immense attention in recent years due to their effective medicinal properties. Aesculus indica is a medicinally important plant being traditionally used for various ailments. The present study aimed to determine the antioxidant and antiproliferative activities of seeds of A. indica. The crude methanolic seed extract was prepared and subjected to sequential fractionation in increasing polarity. The extract and its fractions were investigated for antioxidant activities using various in vitro assays. Further, the extract along with its potential antioxidant fractions were analyzed for their cytotoxic activity against HepG2, human hepatocyte carcinoma cells through bioassays. The results showed highly significant antioxidant potential of methanolic extract of A. indica seeds and two of its fractions prepared with chloroform and ethyl acetate. The studies on hepatocyte carcinoma cells further revealed that the extract and two of its potential antioxidant fractions significantly induced cytotoxicity and inhibited migration, proliferation, clonogenicity and 3D growth of HepG2 cells. It is therefore, concluded that A. indica possess significant antioxidant and cytotoxic potential against HepG2 cells and with further research can be proposed for therapeutic interventions.