Humans are exposed to microplastics (MPs) daily via ingestion and inhalation. It is not known whether this results in adverse health effects and, if so, at what levels of exposure. Without epidemiological studies, human cell in vitro MP toxicological studies provide an alternative approach to this question. This review systematically synthesised all evidence and estimated thresholds of dose–response relationships. MEDLINE and Web of Science were searched from inception to March 2021 and study quality was rated using a novel risk of bias assessment tool. Seventeen studies were included in the rapid review and eight in the meta-regression. Four biological endpoints displayed MP-associated effects: cytotoxicity, immune response, oxidative stress, barrier attributes, and one did not (genotoxicity). Irregular shape was found to be the only MP characteristic predicting cell death, along with the duration of exposure and MP concentration (μg/mL). Cells showed varying cytotoxic sensitivity to MPs, with Caco-2 cells (human adenocarcinoma cell line) being the most susceptible. Minimum, environmentally-relevant, concentrations of 10 μg/mL (5–200 µm), had an adverse effect on cell viability, and 20 μg/mL (0.4 µm) on cytokine release. This work is the first to quantify thresholds of MPs effects on human cells in the context of risk assessment.