<p>Sepsis remains a highly critical and frequent condition in intensive care units, often leading to systemic inflammatory responses, immune suppression, and multiple organ dysfunction. Recent evidence has established pyroptosis, a type of pro-inflammatory programmed cell death, as a key mechanism in the development and progression of sepsis. This process is mediated by inflammasome activation, resulting in cell swelling, membrane rupture, and the release of pro-inflammatory cellular contents that amplify inflammatory cascades. Mesenchymal stem cells (MSCs), known for their anti-inflammatory, immunomodulatory, and tissue-regenerative capacities, have attracted attention as a promising therapeutic approach for sepsis. This review summarizes the mechanistic involvement of pyroptosis in septic pathogenesis and highlights recent advances in MSC-based therapies that target pyroptotic pathways, with the goal of elucidating the potential role of MSCs in the management of sepsis.</p>