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Microplastics (MPs) are ubiquitous anthropogenic contaminants, and their abundance in the entire ecosystem raises the question of how far is the impact of these MPs on the biota, humans, and the environment. Recent research has overemphasized the occurrence, characterization, and direct toxicity of MPs; however, determining and understanding their genotoxic effect is still limited. Thus, the present review addresses the genotoxic potential of these emerging contaminants in aquatic organisms and in human peripheral lymphocytes and identified the research gaps in this area. Several genotoxic endpoints were implicated, including the frequency of micronuclei (MN), nucleoplasmic bridge (NPB), nuclear buds (NBUD), DNA strand breaks, and the percentage of DNA in the tail (%Tail DNA). In addition, the mechanism of MPs-induced genotoxicity seems to be closely associated with reactive oxygen species (ROS) production, inflammatory responses, and DNA repair interference. However, the gathered information urges the need for more studies that present environmentally relevant conditions. Taken into consideration, the lifestyle changes within the COVID-19 pandemic, we discussed the impact of the pandemic on enhancing the genotoxic potential of MPs whether through increasing human exposure to MPs via inappropriate disposal and overconsumption of plastic-based products or by disrupting the defense system owing to unhealthy food and sleep deprivation as well as stress. Overall, this review provided a reference for the genotoxic effect of MPs, their mechanism of action, as well as the contribution of COVID-19 to increase the genotoxic risk of MPs. [Display omitted] • The genotoxic effects of MPs are determined in somatic cells of aquatic organisms and human peripheral lymphocytes. • The mechanism of MPs-induced genotoxicity is associated with oxidative stress, inflammation, and DNA repair disruption. • The COVID-19 pandemic contributes to the genotoxic potential of MPs. [ABSTRACT FROM AUTHOR]