Background: In this review, we evaluated the clinical efficacy of interventions used for the treatment of endo-perio lesions (EPL). Methods: A systematic scoping review of clinical trials was developed. Results: Seven clinical trials were studied. In at least one study group of six of the seven evaluated trials, endodontic and periodontal treatments were performed simultaneously. All trials showed improvement in probing depth in the studied groups; nevertheless, the experimental groups of five studies demonstrated a statistically significant reduction in this parameter. An increase in clinical attachment level was also reported (p < 0.05). Most trials reported an increase in the filling of the bone defect following therapy (p < 0.05). Mechanical periodontal therapy implemented simultaneously with endodontic therapy demonstrated efficacy in the treatment of concurrent EPL without communication. Endodontic treatment and immediate periodontal surgery did not affect the result of the management of combined EPL with apical communication. The use of diode laser, the management of platelet-rich fibrin (PRF) and titanium-prepared PRF, and the implementation of bone grafts plus endodontic treatment with mineral-trioxide or gutta-percha seems to be an adequate strategy in patients with EPL. Conclusions: The treatment of EPL using simultaneous endodontic and periodontal therapies seems to be an acceptable treatment alternative.