Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [−1.46–2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting.