Derivatives of phosphonoamide and phosphonocaprolactam are well-known for their extensive uses in industrial and medical settings. This has raised worries regarding their toxicity to aquatic life as well as their fate in the ecosystem. Thus, for seven days, biomarkers of oxidative stress, neurotoxicity, and metal accumulation were assessed in clams Ruditapes decussatus exposed to 20 and 40 μg/L of N-(2-(diphenylphosphoryl)-2-(thiophen-2-yl) ethyl) acetamide, N-(2-(diphenylphosphoryl)-2-(furan-2-yl) ethyl) acetamide, N-(2-(diphenylphosphoryl)-2-phenylethyl) acetamide, and 7-((diphenylphosphoryl) (phenyl)methyl) azepan-2-one. The results of the metals content analysis indicate that phosphonoamide and phosphonocaprolactam caused metal dyshomeostasis in the digestive gland and gills of clams, with greater levels of zinc and copper detected in the digestive glad following exposure. Phosphonoamide and phosphonocaprolactam derivatives activated biomarkers of oxidative stress, such as GSH, CAT, and MDA, in an organ, concentration, and biomarker dependent manner, exhibiting distinct antioxidant patterns in the digestive glands and gills. By the time the exposure period for both types of phosphorus compounds came to a conclusion, neurotoxic effects were evident in the form of AChE inhibition. Our results demonstrate that filter-feeding species should be taken into consideration when assessing the overall toxicological impact of phosphorus compounds in the aquatic environment. Overall, this exploration was anticipated to yield insights into the distinct responses triggered by these compounds and offer a deeper understanding of the toxicity mechanisms associated with phosphonoamide and phosphonocaprolactam. Additionally, the study highlights the necessity for continuous monitoring of potentially toxic phosphorus compounds in edible marine species to avoid possible repercussions of seafood consumption on human health.