Objective: To compare the Clinical Practice Guidelines (CPG) for pharmacological management of type 2 diabetes (T2D), in Latin America (LA) with international reference guidelines. Method: This systematic review selected three CPG as comparators: the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) and the Latin American Diabetes Association (ALAD). Existing CPG in LA were identified in Medline, Embase, grey literature, health ministries and CPG developers websites of the countries included. Two reviewers independently assessed quality of both reference and local guidelines with the AGREE II instrument. Results: 404 citations were identified, 46 were retrieved for full-text review. Finally, 10 LA CPG remained for the analysis. The ADA CPG scored >80% in AGREE II domains and was selected as the main comparator. 80% of LA CPG were developed before 2018; all of them using public funding. The highest scoring domain according to AGREE II was “scope and purpose” (84%; range 39–100%). The poorest domain was “applicability” (57%; range 6–96%). In overall, six CPG were classified as highly recommended (score of ≥60% in four out of six domains). Only one CPG was classified as not recommended (all domains <60%). Unlike the ADA, the LA CPG fails to describe specific patient profiles. Six CPG provided recommendations based on the presence of cardiovascular disease. Three CPG included recommendations for overweight patients. Only one CPG included recommendations for patients with renal complications. None of CPG had any recommendation for elderly people specifically. Conclusion: In general, T2D CPG in LA have good quality but are outdated. Important gaps have been found regarding the comparison with the ADA CPG. Therefore, there are improvement opportunities for the LA CPG such as including specific patient profiles and having mechanisms that allows their update before three years to keep them current with the best clinical evidence.