In the last few decades, a plethora of studies have focused on human biomonitoring (HBM) of chemical pollutants. Reviewing the copious HBM data reported in these studies is essential for evaluating the effectiveness of pollution management efforts, for example by evaluating time-trends. Nevertheless, guidance to systematically evaluate time trends in published HBM data has never been developed. In this study, we therefore present a proposal for guidelines to conduct “time-trend reviews” (TTRs) that examine time trends in published large HBM datasets of chemical pollutant concentrations. We also demonstrate the applicability of these guidelines through a case study that assesses time-trends in global and regional HBM data on mercury. The recommended TTR guidelines in this study are divided into seven steps: formulating the objective of the TTR, setting up of eligibility criteria, defining search strategy and screening of literature, screening results of search, extracting data, analysing data, and assessing certainty, including the potential for bias in the evidence base. The TTR guidelines proposed in this study are straightforward and less complex than those for conducting systematic reviews assessing datasets on potential human health effects of exposure to pollutants or medical interventions. These proposed guidelines are intended to enable the credible, transparent, and reproducible conduct of TTRs. © 2021 The Author(s)