<p>Plastic pollution has become a global crisis with massive levels of plastic waste infiltration from the highest mountains to the deepest oceans. The hazardous environmental impact of plastic pollution and the presence of microplastics (MPs, particles ≤ 5&#xa0;mm) in mammalian organs have become increasingly evident in recent years. The studies on the adverse health effects of MPs exposure have accelerated, with a lack of evidence related to MPs exposure and spread of infectious diseases. The present review aims to compile research studies on the accumulation of MPs in various organs of the mammalian system, their toxic health effects, associated cellular responses and molecular events to establish a connection between MPs exposure and infectious disease. An additional essential aspect i.e. the toxic impact of co-exposure to MPs with other environmental toxicants and its associated molecular mechanisms, is also highlighted. Predictive molecular links between microplastic exposure and infectious disease were observed for both mouse- and human-specific data. Interestingly, findings indicate that MPs have the potential to alter genes expression related to critical regulatory pathways for infectious disease. The association of MPs exposure with the infectious disease related pathways could suggest that these pathways could be the potential targets of MPs-associated predisposition of infectious disease. This prediction of molecular mechanistic link requires significant experimental validation; however, this review opens a new horizon for assessing long-term infectious disease risks following MPs exposure and the development of effective intervention strategies.</p>