Chitosan, a naturally occurring cationic polymer, has various pharmaceutical utilizations, including drug delivery. The primary amino groups present in the chitosan trigger many vital functions, such as mucoadhesion and mucopenetration, controlled drug release, in situ gelation, transfection ability, and inhibition of efflux pump. Transdermal drug delivery systems have emerged as promising approaches for delivering drugs with poor oral bioavailability and hydrophobic nature than traditional oral delivery systems. It gained popularity due to its noninvasiveness, simple access and removal, sustained drug delivery for prolonged periods, bypassing hepatic first-pass metabolism, higher bioavailability, etc. Furthermore, chitosan has been incorporated as an adjuvant to enhance skin penetration. Moreover, chitosan-based drug delivery systems are demonstrated as a potential candidate for transcending the barriers of the eye, improving bioavailability by its mucoadhesive property, enhancing corneal permeability, and prolonging residence time at the target site. This chapter has emphasized topics such as the chitosan and its physicochemical properties; barriers related to topical, transdermal, and ocular delivery; applications of various chitosan-based formulations, which include nanoparticles, nanocapsules, gels, microneedles, patches, and contact lenses; and lastly its regulatory status.