Micro and nanoplastics, pervasive environmental pollutants, pose significant threats to ecosystems and human health, necessitating urgent research and innovative solutions. Several research groups have investigated the uptake of synthetic microplastics (MPs) and nanoplastics (NPs) using various model organisms. We investigated the uptake and the growth inhibitory effect of polystyrene (PS) and polymethacrylate (PMA)-based MPs and NPs in Tetrahymena pyriformis. Carboxyl-modified PS-MPs showed a greater growth inhibitory effect than amine-modified PS-MPs and PMA-based MPs. We also studied the impact of these particles on the transcriptomics of T. pyriformis and observed that PS-MPs directly impact various signaling pathways related to oxidative stress. PMA-based MPs showed differential expressions of signaling pathways related to cancer and some related to oxidative stress. Using a fluorescent probe, we measured the reactive oxygen species (ROS) generated by carboxyl-modified PS-MPs and PMA-MPs and observed that PS-MPs generated greater ROS than PMA-MPs. This study suggests that it is important to understand the type and the nature of chemical modification of various MPs and the specific signaling pathways in particular oxidative-related pathways they target on diverse groups of organisms, as this will provide key information related to the effect of various modified MPs and NPs on human health.