Objective: The present investigation was aimed towards developing calcium crosslinked derivative of carboxymethylated cassia fistula gum and crosscarmellose sodium based orodispersible tablets (ODTs) of propranolol hydrochloride for enhancing the bioavailability and efficacy. Methods: Orodispersible tablets (ODTs) of propranolol hydrochloride was formulated using natural (a carboxymethylated derivative of cassia fistula gum) and synthetic polymer (crosscarmellose sodium) by wet and dry granulation, lyophilization and cotton candy methods and then finally compressed by direct compression. The prepared ODTs were evaluated for several parameters such as hardness, friability, in vitro disintegration time, in vitro drug release. In vivo and stability studies were carried out on optimized formulation coding PC1. Results: Drug polymer interaction were judged by FT-IR, DSC and XRD. The optimized formulation coding PC1 prepared by cotton candy process containing 2.5% w/w of crosslinked cassia fistula gum has the least disintegration time (18.9±0.4s), weeting time (12.5±0.8s) and relased the drug of 88.2% within 10 min in contrast to croscarmellose sodium. In vivo absorption studies revealed that same formulation has Cmax (µg/ml) 2.13±0.73, tmax (h) 0.21±0.17 and AUC∞0 (µg ml-1 h-1) 14.33±1.59. Conclusion: This research manuscript clearly shows the successful development of the ODTs loaded with an antihypertensive drug, namely propranolol hydrochloride. The formulation developed by cotton candy process utilizing crosslinked cassia fistula gum as a natural superdisintegrant in contrast to other existing techniques can be a best option over synthetic superdisintegrant i.e. crosscarmellose sodium. The prepared ODTs was enhanced the absorption rate by lowering tmax, which inturn enhance the bioavailability and the efficacy of drug.