In this study, niosome formulations were prepared and evaluated for their effects on improving the oral bioavailability of paclitaxel (PCT). Niosomes were prepared from Span 40 and coated with bioadhesive carbopol polymers. The niosomes encapsulated 98.7% ± 0.8 of the initially added PCT and their size ranged from 133 ± 6 nm to 320 ± 6 nm. The stability of Carbopol 974P coated niosomes in bile salts was better than uncoated niosomes. Extended release of PCT was observed. After oral administration of formulations to Wistar rats, higher drug plasma concentrations were observed for niosomes comparing to PCT suspension. The high PCT accumulation in intestine and liver obtained after Carbopol 974P coated niosomes administration indicated their potential regarding effective treatment of localized carcinomas in intestine and liver. The relative bioavailability of PCT was increased 3.8- and 1.4-fold by uncoated and Carbopol 974P coated niosomes emphasizing the ability of niosomes on improving the oral bioavailability of PCT.