A microcosm experiment was carried out to provide a deeper insight into the toxic mechanisms exerted by two lipid regulator agents, as well as their interactions with the polyvinyl chloride microplastic on marine meiofauna. Two concentrations of Atorvastatin “A” and of Simvastatin “S”, (i.e., 0.6 mg.kg−1 and 6 mg.kg−1), as well as a single dosage of polyvinyl chloride microplastics “P” at 20 mg.kg−1, separately and their combined mixtures (“AP” and “SP”) were used on coastline dwelling marine meiofauna, with a main focus on nematodes. The results showed a significant reduction in meiofauna abundance in treatments compared to control. SIMPER analysis highlighted a significant decrease in the abundance of epigrowth feeders (2A), which possess conical (co) tails, and indistinct (id) amphideal foveas compared to control microcosms, reflected mainly in the decrease in abundance of the species Prochromadorella longicaudata. Furthermore, the contamination with microplastic affected only the omnivores-carnivores guild. Another finding of the current experiment is that the mixtures of microplastic with drugs lead to synergic interactions that increased their toxic effects on marine nematode communities.