Tissue transglutaminase (TG2) is a multifunctional protein that functions as a protein cross-linking enzyme and also as an intracellular G-protein. It has been implicated in numerous disorders such as celiac disease, fibrosis and different cancers. Due to these diverse pathologies, there is a need to develop a range of inhibitors that can target the different functionalities of TG2. In this review, we present the latest inhibitors published over the past decade, specifically focussing on irreversible inhibitors (peptidomimetic and small-molecule), probes, and reversible inhibitors.