The thiazolidinedione 49 (TD 49) is an effective algaecide against harmful algae; however, its potential effects on the immune function of the edible bay scallop are unclear. Therefore, the present work studied the effects of TD 49 on the immune response in bay scallop by evaluating activities of acid phosphatase (ACP), alkaline phosphatase (ALP), and superoxide dismutase (SOD), as well as nitric oxide (NO) levels, total protein content, and expression of immune genes ( CTL-6, PGRP, PrxV, MT, and Cu/Zn-SOD) at 3–48 h post-exposure (hpe) to TD 49. The activities of ACP and ALP significantly increased in TD 49-treated groups at 3–24 hpe, whereas NO levels decreased significantly in 0.58 and 0.68 μM of TD 49 at 6–24 hpe, after which the level was similar to that in the untreated control. Moreover, SOD activity significantly increased in all three concentration groups at 3–6 hpe, while it decreased at 12 hpe in the 0.68 μM TD 49 treatment group. Notably, total protein content increased with TD 49 treatment at each time interval. The results revealed that variable effects on the expression of immune-related genes were observed after treatment with TD 49. The findings demonstrate that exposure of scallops to TD 49 changes immune responses and expression of immune-related genes. We hypothesize that TD 49 may disrupt immune system in bay scallop. The current investigation highlights the potential negative effects of using TD 49 as an algaecide on marine economic bivalves to control harmful algal blooms in marine environments.