In present study, tragacanth gum-based pH-responsive tunable drug delivery devices have been synthesized. The relation between synthetic reaction parameters during polymerization reaction and swelling and drug release from polymers has also been studied. Polymers were characterized by FTIR, blood compatibility and swelling studies. Swelling of TG-cl-poly(AAm) polymers decreased with an increase in feed monomer [AAm] and cross-linker [NN-MBA] concentration. Polymer showed pH-responsive swelling nature as swelling increased with an increase in pH of solution. The swelling and drug release occurred through non-Fickian diffusion mechanism and release profile obey Korsmeyer–Peppas model of drug release. There is no rapid increase in drug release rate from drug-loaded polymers which is a required characteristic for controlled drug delivery system. TG-cl-poly(AAm) polymers are found to be non-thrombogenic, haemo-compatible during blood-compatibility studies. These polysaccharide based polymers can be tailored for developing site-specific biocompatible delivery devices to enhance local and systemic bioavailability of loaded curative agents.