Background e-Waste is a rapidly growing waste stream worldwide, and Bangladesh is a hub of e-waste handling. Informal e-waste recycling operations involve crude methods for dismantling, repairing, sorting, and recycling electronic goods with bare hands and without personal health protections. Direct inhalation or dermal exposure to toxicants during informal recycling is common. Evidence suggests that e-waste–derived toxicants pollute the terrestrial ecosystem and have been linked with adverse health effects. However, e-waste recycling–related occupational health hazards have not been adequately explored in the context of Bangladesh. Objective Our study aims to expand the current understanding of exposure to e-waste. This study will measure the metal concentrations in biological and environmental samples and evaluate the relationship between heavy metals and the biochemical systems of the e-waste workers. Methods The study uses a cross-sectional study design consisting of an exposed site and a nonexposed control site. The trained team collected information on individual exposures, detailed work and medical history, and biological samples (blood, urine, and hair) from each subject. This study will measure heavy metal levels (lead, cadmium, and mercury) and biochemical parameters (hematological, hormonal, renal, and others) from the biological samples with reported physical function as outcomes of interest. In addition, we also collected soil and dust samples from both exposed and nonexposed control sites to measure the health risk. All the environmental samples will be analyzed using inductively coupled plasma mass spectrometer to determine metal concentrations. We will also conduct a qualitative investigation for a deeper understanding of the e-waste management system in Bangladesh. Results The protocol has been approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh, and The University of Queensland’s Human Behavioral Ethics Committee. Informed written consent was obtained from all participants. We recruited 199 workers from the e-waste sites with at least 5 years of exposure and 104 control subjects with no industrial or e-waste exposure. Sample analysis is estimated to be completed in 2022. Conclusions Although many studies have identified potential adverse health outcomes from exposure to e-waste, there is a lack of published epidemiological research in Bangladesh. Research in this field is particularly pressing in the context of the current e-waste trend and the need to deepen the understanding of exposures and outcomes. International Registered Report Identifier (IRRID) DERR1-10.2196/38201