Plastic microparticles, a form of microparticles commonly referred to as microplastics (MP), have been the focus of increasing interest for understanding potential human and ecological impacts, including the development of health-based benchmark values. This systematic review critically evaluates 24 mammalian studies reporting reproductive and developmental outcomes, a disproportionately focused research area, with a particular focus on methodological rigor and risk of bias. Fit-for-purpose aspects of selection, performance, and attrition bias were integrated into the critical appraisal to better understand the potential bias studies may have across these domains. All studies received a Tier III rating based on the National Toxicology Program’s Office of Health Assessment and Translation (NTP OHAT) framework, indicating a high risk of bias and insufficient reliability for risk assessment. Key issues identified across the body of evidence include poor exposure characterization, inadequate outcome assessment, lack of validated test guidelines, and failure to account for critical reproductive parameters such as estrous cycle monitoring and sperm analysis standards. Additionally, discrepancies in the particle characterization and homogeneity of the test material limit comparability and reproducibility across studies. This work highlights the current limitations in the body of evidence in terms of internal and construct validity, which precludes any conclusions on MP-related reproductive toxicity, and details a path forward for investigators to consider in future research.