A major challenge associated with the oral delivery of anti-hypertensive drugs is their poor water solubility and low oral bioavailability. Carvedilol (CAR), a potential beta-blocker is hydrophobic drug that exhibit limited therapeutic effect through oral conventional drug delivery systems. For this reason, it is prerequisite to further investigate and develop an alternative drug delivery system so as to improve therapeutic efficacy of carvedilol as well as to minimize side effects of conventional treatment therapy. In the present study, it was aimed to develop nanoparticles (NPs) of a hydrophobic antihypertensive agent, Carvedilol by using chitosan (CS) as biodegradable polymer. Carvedilol chitosan nanoparticles (CAR-CS-NPs) were prepared by ionic gelation technique using sodium tripolyphosphate (TPP) as a crosslinking agent. The NPs were optimized and validated by Box-Behnken design (BBD). The optimized formulation showed particle size 102.12 nm and drug entrapment efficiency 71.26 ± 1.16%. The drug release profile of CAR-CS NPs showed biphasic release pattern with an initial burst release in the first 2 h followed by a controlled release over a period of 72 h. The pharmacokinetic results revealed that the optimized chitosan nanoparticles formulation have higher bioavailability than marketed tablet formulation which indicates CAR-CS NPs as an effective strategy to delivery poorly water soluble drugs.