The synergistic impact of microplastics (MPs) and organic pollutants remains poorly understood in the marine environment. This study aimed to assess the toxicity of polypropylene microplastics (PS) and/or di-(2-ethylhexyl) phthalate (DEHP) on marine clams. Both Ruditapes philippinarum and Tegillarca granosa were exposed to PS and DEHP individually and combined at environmentally relevant concentrations for 48 h. The filtration rate, antioxidant enzymes activity, lipid peroxidation, reactive oxygen species accumulation, and histological alterations were evaluated. Our results show that single or co-exposure to MPs and DEHP significantly decreases the filtration rate in both type of clams, but the latter exhibited stronger inhibition effect. Close examination of accumulation of reactive oxygen species and related biomarkers revealed that combined exposure exerts greater oxidative stress in the cells, which causes more serious histopathological damage in the gills of the bivalves. Our study implies that MPs, in synergy with organic pollutants, can be more harmful for marine organisms.