In recent years, polypropylene microplastic has persisted in freshwater ecosystems and biota, forming ever-growing threats. This research aimed to prepare polypropylene microplastics and evaluate their toxicity to the filter feeder Oreochromis mossambicus. In this research, fish were given a dietary supplement of polypropylene microplastics at 100, 500, and 1000 mg/kg for acute (96 h) and sub-acute (14 days) durations to assess toxic effects on liver tissues. FTIR results revealed the presence of polypropylene microplastic in their digestion matter. The ingestion of microplastics in O. mossambicus led to fluctuations in homeostasis, an upsurge in reactive oxygen species (ROS) levels, an alteration in antioxidant parameters, including superoxide dismutase (SOD), catalase (CAT), glutathione-S–transferase (GST), and glutathione peroxidase (GPx); a promotion in the oxidation of lipid molecules; and a denaturation in the neurotransmitter enzyme acetylcholinesterase (AChE). Our data indicated that sustained exposure to microplastics (14 days) produced a more severe threat than acute exposure (96 h). In addition, higher apoptosis, DNA damage (genotoxicity), and histological changes were found in the liver tissues of the sub-acute (14 days) microplastics-treated groups. This research indicated that the constant ingestion of polypropylene microplastics is detrimental to freshwater environments and leads to ecological threats.