We have prepared tinidazole (TNZ) functionalized biodegradable chitosan (CH)/poly (epsilon-caprolactone) (PCL) mucoadhesive hybrid nanofiber membrane (TNZ-PCHNF) to alleviate existing shortcomings in treatment of periodontitis. Box-Behnken design was employed for evaluating influence of formulation and processing variables on quality of final formulation. Optimized nanofiber membrane was subjected to solid-state and surface characterization studies using FTIR, DSC, XRD, SEM and AFM, which revealed that TNZ was entrapped in an amorphous form inside smooth and uniform cylindrical nanofibers without any physicochemical interaction with excipients. The optimized TNZ-PCHNF membrane had a diameter of 143.55 +/- 8.5 nm and entrapment efficiency of 83.25 +/- 1.8%. In vitro drug release and antibacterial study-demonstrated capability of the developed nanofiber membranes for efficiently delivering TNZ in a sustained manner up to 18 days, and its ability to inhibit bacterial growth, respectively. Further, reduction of contact angle (from 123.4 +/- 2.5 to 27.4 +/- 2.3) revealed that blending of CH with PCL increases hydrophilicity of the nanofiber membrane. MTT assay and CLSM study suggested that nanofiber membrane was devoid of cytotoxicity on mouse fibroblasts. Moreover, preliminary clinical trials on patients proved therapeutic efficacy of the nanofiber membrane by eliciting a significant (p <0.05) decrease in clinical markers of periodontitis. (C) 2017 Elsevier B.V. All rights reserved.