Fish are a staple and inexpensive food source that is rich in animal protein, along with various vitamins, essential amino acids, and minerals; exposure to microplastics, pesticides, and various nanoparticles generates reactive oxygen species (ROS) and induces oxidative stress, inflammation, immunotoxicity, genotoxicity, and DNA damage; it also alters the gut microbiota, which in turn affects the Nrf-2, JNK, ERK, NF-κB, and MAPK signaling pathways; and Nrf2-KEAP1 signaling modulates redox status marinating enzymes in fish. These contaminants are emerging contaminants in the marine biota. This chapter summarizes the oxidative stress caused by microplastics, pesticides, and nanoparticle contamination or exposure in fish habitat water and their impact on human health. A decrease in fish nutritional quality and population has a significant impact on the human diet, influencing traditions and economics worldwide. However, traces of microplastics and nanoparticles in the habitat water can enter humans by consuming contaminated fish, which may result in serious health hazards. In order to protect fish health from stress, the contribution of nano-technology or nano-formulations was investigated.