This systematic review aimed to evaluate the efficacy of clear aligner therapy (CAT) in leveling the curve of Spee (CoS) in adult patients with permanent dentition. The clinical relevance of CoS correction lies in its impact on overbite reduction, occlusal function, and overall treatment outcomes. A comprehensive literature search was conducted across five electronic databases (PubMed, Scopus, Cochrane Library, Embase, and Web of Science), supplemented by grey literature. Eligible studies were retrospective clinical investigations assessing changes in CoS with CAT. Two reviewers independently performed data extraction and risk of bias assessment using the ROBINS-I tool, while the quality of evidence was graded using the GRADE approach. Seven retrospective studies met the inclusion criteria. All reported a reduction in CoS depth after CAT, ranging from 0.01 mm to 2.2 mm. Anterior intrusion was achieved to a limited extent, while posterior extrusion was inconsistent and often poorly expressed. Overbite reduction was observed in some studies, but none provided data on long-term stability. The predictability of CoS correction varied widely from 35% to 72%. All studies were judged to have a serious risk of bias, and the certainty of evidence was rated as low to very low. CAT appears capable of reducing CoS depth with outcomes comparable to fixed appliances; however, vertical control, especially posterior extrusion, remains unpredictable. In clinical practice, aligners may be considered for mild to moderate CoS correction, provided limitations are acknowledged. Further high-quality prospective trials with standardized protocols and long-term follow-up are required to strengthen the evidence base.