Thiazolidinone derivatives (TDCs) were prepared by converting chitosan into chitosan's Schiff's bases (CSBs), followed by treatment with mercaptoacetic acid. Both CSBs and TDCs were tested for antimicrobial activity against four different bacteria. All TDCs showed comparatively better anti-microbial activity without much affecting basic physical properties of chitosan such as film-forming capacity, tensile strength, etc. This indicates that chitosan derivatives with a thiazolidinone moiety might be a better material for wound dressing.