This paper reports the synthesis of 28 thiazolidinedione derivatives along with their algicidal activity against microalgae causing harmful algal blooming. Among the 28 compounds tested, most showed effective algicidal activity against Heterosigma akashiwo, Chattonella marina, and Cochlodinium polykrikoides, while non-harmful algae were relatively tolerant to these thiazolidinedione derivatives. Compounds 6, 13, and 22 were the most potent against C. polykrikoides with IC50 values <0.5 mu M. Among the thiazolidinedione derivatives tested, compounds 7, 13, 27, and 28 were extremely competent and selective to C. polykrikoides with 1050 values ranging from 0.1 to 2 mu M, while C. marina and H. akashiwo showed an IC50 value ranging from 30 to 130 mu M. These results show that some thiazolidinedione derivatives can act as potent algicides against harmful algal blooms.