The prevalent use of nanoparticles has adverse negative effects on biosystems. Subsequently, this study aimed to use Caelatura nilotica to assess the ecotoxicity of TiO2 NPs and how Dimercaptosuccinic acid (DMSA) improves these effects. Two concentrations of TiO2 NPs (25 and 150 µg/L) were used for 28 days. TiO2 NPs bioaccumulation, gonadal weight, gonado‐somatic index, and histopathological alterations of gonads were determined. The tissues’ accumulation of TiO2 NPs was concentration‐time‐dependent: it was 78.5 ± 28.93 μg/g dry weight in the exposed clams to 150 µg/L TiO2 NPs after 4 weeks of exposure. The gonadal weight and gonado‐somatic index significantly decreased of the exposed group to 150 µg/L TiO2 NPs over the experimental period that they ended with values (1.01 ± 0.57 gm, 19.15 ± 7.75%, respectively). There are some histological alterations in the gonads of C. nilotica such as necrosis, deteriorated connective tissue, increased fibrous tissue, a reduced presence of mature sperms and mature ova, and irregular shapes of testicular/ovarian follicles. When using Dimercaptosuccinic acid (DMSA), this led to a reduction in accumulation of TiO2 NPs by the end of the experiment. So, C. nilotica is a promising model to reflect the adverse nano‐toxics. DMSA emerges as a potentially valuable chelating agent that abolishes the negative effects of these nanoparticles.