Sepsis is a life-threatening disease caused by the overwhelming response to pathogen infections. Currently, treatment options for sepsis are limited to broad-spectrum antibiotics and supportive care. However, the growing resistance of pathogens to common antibiotics complicates treatment efforts. Excessive immune response (i.e., cytokine storm) can persist even after the infection is cleared. This overactive inflammatory response can severely damage multiple organ systems. Given these challenges, managing the excessive immune response is critical in controlling sepsis progression. Therefore, Mesenchymal stem cells (MSCs), with their immunomodulatory and antibacterial properties, have emerged as a promising option for adjunctive therapy in treating sepsis. Moreover, MSCs exhibit a favorable safety profile, as they are eventually eliminated by the host's immune system within several months post-administration, resulting in minimal side effects and have not been linked to common antibiotic therapy drawbacks (i.e., antibiotic resistance). This review explores the potential of MSCs as a personalized therapy for sepsis treatment, clarifying their mechanisms of action and providing up-to-date technological advancements to enhance their protective efficacy for patients suffering from sepsis and its consequences.