The human body is exposed to the ingestion of microplastics that are often contaminated with other substances, which can be released into our body. In this work, a dynamic in-vitro simulator of the gastrointestinal tract based on a membrane reactor has been used for the first time to study the release, bioaccessibility, and bioavailability of chromium (Cr) and lead (Pb) from polyethylene and polypropylene microplastics previously contaminated in the laboratory. The results showed that 23.11% of the initial Cr and 23.17% of the initial Pb present in microplastics were able to cross the tubular membrane, simulating the intestinal absorption phase. The pH evolution during the gastric phase and the duodenal phase, the interaction mechanisms with physiological fluids, and the properties of the polymers, such as specific surface, porosity, and/or surface degradation, affected the kinetics of release from the microplastics and the behavior of both heavy metals. Cr was released very early in the gastric phase, but also began simultaneously to precipitate quite fast, while Pb was released slower and in less quantity than Cr, and did not precipitate until the beginning of the duodenal phase. This study shows, for the first time, how useful the dynamic gastrointestinal simulator is to study the behavior of microplastics and some problematic heavy metals along the human gastrointestinal tract, and can serve as a reference for future studies focused on the effects of these substances in the human body.