Global manufacturing and utilization of medium-chain chlorinated paraffins (MCCPs) continue to rise due to the increasing regulation on short-chain chlorinated paraffins (SCCPs). Accumulating evidence reveals that MCCP levels in various environmental matrices and foodstuffs have surpassed SCCP levels. Importantly, MCCPs have been detected in multiple human biospecimens, including maternal and cord blood, breast milk, hair, and nails, suggesting unavoidable human exposure risks. However, existing studies investigating the toxicity of CPs have predominantly focused on SCCPs rather than MCCPs. The potential toxicological profiles of MCCPs including hepatotoxicity, nephrotoxicity, and thyroid dysfunction, which were revealed in several early high-dose experimental studies, should be reassessed at environmentally relevant doses. Furthermore, potential sensitive toxicological endpoints such as lipid and glucose metabolism dysregulation should be investigated. Comprehensive toxicological studies of MCCPs at environmentally relevant doses are critically required to evaluate whether MCCPs represent safe alternatives to SCCPs and to provide novel toxicological parameters for recalibrating reference doses in human risk assessments.