Carbamazepine (CBZ) and methylmercury (MeHg) are pervasive contaminants that share molecular toxicity pathways (e.g., neurotoxicity, oxidative stress, energy metabolism) and, in addition to their main toxicity target, are both suspected of reprotoxicity. Yet, the precise mechanisms behind these putative effects remain a subject of ongoing investigation. Dreissena polymorpha holds great potential for freshwater biomonitoring due to its wide distribution and filter-feeder lifestyle, but the influence of the reproductive stage for the biological response to pollutants is still understudied. Here, D. polymorpha males in the proliferation and maturation reproductive stages were exposed for 24 h to CBZ, MeHg and CBZ+MeHg. We combined the comet assay, proteomics and targeted RT-qPCR approaches to evaluate the impact of those exposures on the gonads. In the proliferation stage, both single and co-exposures modulated transcripts involved in antioxidant defenses. In the maturation stage, no significant modulation was observed with targeted approaches, most likely due to a higher background level masking the effect of pollutants. At both stages, differentially abundant proteins were involved in similar metabolic pathways, including the energy metabolism, antioxidant defenses and gonadal cell development. Proteomics also revealed modulation of proteins involved in genotoxicity pathways exclusively in the proliferation stage, aligning with the observation of an increase in genotoxic damage. MeHg exposure caused more alterations than co-exposure, in contrast with previous studies on other organs during similar exposure in D. polymorpha. This underlined the importance of assessing organ-specific responses to pollutants. Moreover, data confirmed a newly identified reprotoxic effect of MeHg, reinforcing the need to better consider the reproductive stage in biomonitoring programs using this species, and species with similar characteristics.