Any enhanced or modified cement or endodontic sealers must be examined to make sure its qualities meet standards before recommending its usage in therapeutic settings. Aims: To evaluate and compare the Cytotoxicity, solubility, and setting time of endodontic sealers with and without incorporation of chitosan nanoparticles(CsNPs) and chlorhexidine(CHX). Settings and Design: Experimental non clinical trial, in-vitro study. Methods and Material: Samples were divided into following groups with 24 samples in each group: Group A: AH Plus Sealer, Group B: AH Plus Sealer + CsNPs +CHX, Group C : CeraSeal sealer, Group D: CeraSeal sealer + CsNPs +CHX Materials and methods. Cytotoxicity testing was done using MTT assay, setting time (ST) was measured by using Vicat apparatus and solubility testing was done by weighing the set samples before ageing, at day 1, day 7 and day 30 on a digital weighing balance.