This chapter explores the mechanism of the fabrication of polysaccharide-based nanocarriers and their application as potential drug delivery vehicles for local and systemic action. The remarkable features of polysaccharides offer enormous potential for their applicability in the designing of drug delivery systems. Skin comprises of two major layers, dermis and epidermis. The epidermal layer comprises mainly of stratified keratinocytes, in which the stratum corneum (SC) cells or corneocytes remains immersed in a proteinaceous covering, with an outer lipid covering, encompassed by an extracellular lipid matrix. Due to their versatile functions, the skin may also act as a chemical or metabolic barrier, where enzymes are present in the basal layer of the viable epidermis, the extracellular region of the SC layer, and also the appendages in the dermal layer. The transdermal polysaccharide-based nanocarriers that have gained more attention by the researchers are nanoparticles and nanofibers.