Hyperbranched chitosan (HPCN) has been synthesized from the polycondensation route and transformed into an oral thin film (HCTF) and nanofiber (HCNF) formulation with the addition of donepezil drug. Chitosan blended hyperbranched polyester (HBPE) prepared and formulated as a nanofiber (CNHPN) and thin film (CNHPF). Both carried out to process for the treatment of Alzheimer’s disease. Higher thermal stability and porous surface with fiber diameter (110 to 115 nm) observed for hyperbranched nanofiber formulations. Faster disintegration (15 s) of nanofiber (HCNF 2) achieved in vitro drug release about 97.03% of drugs with an interval of 45 min. In vivo animal model studies demonstrated that plasma absorbing maximum concentration (Cmax ) as 18.94 ng/mL for CNHPN 2 formulation at the lowest time-bound (3.3 h). The total are under curve [AUC(0–∞)] of hyperbranched chitosan has faster absorption rate (978.1 ng/mL) than marketed formulation (132.05 ng/mL). These results suggested that chitosan blended/hyperbranched chitosan nanofiber formulation is good alternative with commercial formulations for the treatment of Alzheimer’s disease. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.