Heavy-metal toxicity severely affects agricultural productivity as well as the human health worldwide. Among heavy metals with noticeable noxious effects, mercury (Hg) acts as a potential contaminant, having a crucial impact on natural resources and crop production. Hg-tolerance mechanisms in plants are not very clear. Over the years, proteomics has emerged as a significant tool to explore the plant response and tolerance mechanisms to Hg stress. Proteins are the functional players of cells as they regulate the physiological processes. Hg-induced modulation of proteins has been documented in several plant systems. Identification of key proteins and their roles in Hg tolerance are crucial to produce Hg resistance crops, thus contributing to global food security. Proteomic studies give us a comprehensive idea of protein networks and signalling pathways involved in Hg detoxification. The present review provides an overview of proteomic research about Hg tolerance in the model and non-model plants, offers a broad insight of stress proteins and highlights various proteomic approaches used to identify stress-responsive proteins.