In recent years, the widespread use of bisphenol compounds and microplastics (MP) have attracted attention due to their harmful effects. Here, individual and combined effects of MP and bisphenol compounds, were assessed on adult zebrafish after co-exposure of bisphenol A (BPA) or bisphenol S (BPS) and 25 μm polyethylene MP. Impacts on their offspring (the F1 generation) were also investigated. The reproductive toxicity in adult zebrafish impacted exerted by bisphenol compounds were aggravated by the co-presence of MP. Transcriptomics and metabolomics further showed single or co-exposure of bisphenol compounds and MP could together regulate apoptosis, calcium signaling pathway and glycerophospholipid signaling pathways. Our results also showed the different toxicity mechanisms on transcriptional and metabolic profiles in the combination effects of bisphenol compounds and MP. The co-exposure of BPA and MP predominantly influenced neurotoxicity via the MAPK signaling pathway and voltage-dependent calcium channels, whereas the co-exposure of BPS and MP principally affected visual development through phototransduction and retinol metabolism. The co-exposure of BPA and MP, as well as BPS and MP, specifically regulate lipid metabolism and carbohydrate metabolism in zebrafish offspring, respectively. Overall, this study provided a deep understanding of the toxicity differences between co-exposure and single exposure of bisphenol compound and MP in zebrafish, as well as the transgenerational effects and potential molecular mechanisms of bisphenol compounds and MP in zebrafish offspring.