Microplastics (MPs) and nanoplastics (NPs) have become an important global environmental issue due to their widespread contamination in the environment. This review summarizes existing literature on the effects of MPs/NPs on three important biomarkers including enzymatic activity, gene expression, and histopathology in various organisms from 2016 to 2021 and suggests a path forward for future research. Application of enzymatic activity, gene expression, and histopathology biomarkers are increasingly used in experimental toxicology studies of MPs/NPs because of their early signs of environmental stress to organisms. Between 2016 to 2021, 70% of published studies focused on aquatic organisms, compared to terrestrial organisms. Zebrafish were widely used as a model organism to study adverse impacts of MPs/NPs. Polystyrene (PS) were the most important polymer used in experimental toxicology studies of MPs/NPs. Fewer studies focused on the histopathological alterations compared to studies on enzymatic activity and gene expression of different organisms exposed to MPs/NPs. There is a growing need to better understand toxic effects of environmentally relevant concentrations of MPs/NPs on enzymatic activity, gene expression, and histopathology biomarkers of both aquatic and terrestrial organisms.