The prevalence of heavy metal ion contamination is increasing worldwide—posing a growing threat to both ecological and human well-being. In recent years, there have been significant research endeavors focused on the quantitative analysis of these heavy metal ions. There is an increasing demand for cost-effective, sensitive, selective, and rapid methods for detecting them. In the context of functional materials for detection as well as effective diminution of heavy metal ion, glutathione is recognized as well as widely proven for its’ robust capacity to form complexes with harmful heavy metal ions, with its solubility in water, enduring action, and convenient accessibility. Consequently, glutathione is increasingly being utilized as a preferred molecular probe in the development of highly sensitive, cost-effective, and easily accessible sensors. Keeping in cue of the increasing use of glutathione, this mini-review provides a summary of the findings from different glutathione-based heavy metal ion detection approaches as documented in recent literature. These approaches are classified according to their respective techniques of signal transduction. The discussion and comparison of their operation and execution, as well as the evaluation of figures of merit such as limit of detection, selectivity, and response time, are presented. Likewise, removal mechanisms along with challenges are also briefed in this mini-review.