Microplastics are a globally emerging contaminant in the environment, but little is known about the potential risks of microplastics to human health. Possible exposure routes of microplastics to humans include ingestion, inhalation, and dermal penetration, with the last of these needing equal attention as the other two main routes. Evidence showed the presence of microplastics in human-derived biological samples (i.e., excrement, biofluids, and tissues). Most of the toxicological studies of microplastics on humans were based on laboratory rodents and human-derived cells. Energy homeostasis, intestinal microflora, and the reproductive, immune, and nervous systems were regarded as targets of microplastics. The toxicity of microplastics on microstructures including lysosomes, mitochondria, endoplasmic reticulum, and the nucleus further revealed the potential risks of microplastics on human health at the cellular levels. As a carrier, microplastics also had the potential to magnify the toxicity of other contaminants in the environment (e.g., plasticizer, metals, antibiotics, and microorganisms). Studies of microplastics at environmentally realistic conditions are still in their infancy with many unsolved questions to predict their risks on human health.