Industrial wastewater has become a great concern due to high concentrations of several hazardous contaminants, particularly heavy metals. Heavy metal contamination and its consequences for human health and the environment have gained interest in developing low-cost, long-term cleanup technologies. Biologically based wastewater treatment approaches being more effective than conventional treatment methods are getting more attention recently. Applying natural coagulants in wastewater treatments has progressively improved the coagulation-flocculation process efficiency. The main mechanism for heavy metals removal by coagulation is adsorption; therefore, natural coagulants perform better than chemical coagulants in heavy metals removal as natural coagulants contain biopolymers with active sites for heavy metals adsorption. This systematic review focuses on applying nature coagulants for heavy metals removal from different environmental systems. A systematic and comprehensive search for related articles on Web of Science, PubMed, and Scopus on the use of natural coagulant for heavy metal removal from wastewater was conducted up to May 2022. After examining, extracting and deleting duplicate records, 81 relevant articles containing data on types of natural coagulants, extraction methods of active compounds, mechanisms of metal removal by coagulation process, and the performance of natural coagulants for the removal of heavy metals have been reviewed. Their major findings with technical gaps and possible solutions are summarized. The review is novel as it summarizes the main findings of a series of previously published articles on the role of natural coagulants, particularly the removal of heavy metals. The review also identified gaps and research questions and suggested possible solutions for the successful practical application of natural coagulants in wastewater treatment.