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The main objective of the study was to prepare tamarind seed polysaccharide grafted copolymers of polyacrylamide (TSP-g-Am) using a 3² factorial design. Tamarind seed polysaccharide (TSP) was extracted, and grafted copolymer of TSP was prepared using polyacrylamide as copolymer and ceric ammonium nitrate as initiator. Various batches (F1-F9) of TSP-g-Am were prepared, among which F1 showed highest grafting efficiency; hence, the prepared TSP-g-Am (F1) was evaluated for grafting efficiency, conversion, effect of initiator and further characterized using SEM analysis, contact angle determination, DSC analysis, swelling index, swelling and deswelling, and chemical resistance. The contact angle of TSP was found to be 81 ± 2, and that of TSP-g-Am (F1) was found to be 74 ± 2, which indicates that the wetting ability of the grafted copolymer was less than that of the native polymer. The results of thermal analysis indicated that TSP-g-Am had a more stable molecular structure than TSP. The morphology of the grafted polymer was observed from SEM images, and it was observed that the particles was asymmetrical. Antimicrobial activity was also found in the grafted copolymer. The present study concludes that the TSP-g-Am showed an excellent performance in thermal stability and swelling capacity compared with TSP. The detailed structural characteristics, as well as the excellent thermal stability and swelling capacities, will make it beneficial to use the synthesised copolymer as a precursor for the production of large-scale eco-friendly advanced materials with a wide range of applications, acting as a stabiliser, thickener, binder, release …