Aims: Diabetes mellitus (DM) and atrial fibrillation (AF) commonly co-exist. Oral anticoagulants (OACs) are widely used in patients with DM. This review aims to summarise the available literature on the safety (hypoglycaemia or bleeding) and efficacy (stroke or systemic embolism) of the use of OACs in patients with DM. Methods: We searched the Medline, the Excerpta Medica dataBASE (Embase) and Cochrane databases up to the 10th of December 2020. The search strategy was conducted using both keywords and MeSH terms. We included randomised controlled trials (RCTs) and observational studies that reported on the safety and efficacy of the use of OACs in patients with diabetes from all age groups. Study selection, data extraction and quality assessment were conducted independently by two reviewers. Results: A total of 3,976 articles were identified through the search process, of which seven studies met the inclusion criteria of the systematic review: four observational studies and three studies that were randomised controlled trials, with a total of 703,855 patients. Two observational studies reported that the use of warfarin was associated with a higher risk of hypoglycaemic events, specifically with sulfonylurea. One observational study and three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a higher risk of bleeding. In addition, three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a lower risk of stroke or systemic embolism. Conclusions: This systematic review found that DOACs had a better efficacy outcome and safer clinical outcomes in comparison to warfarin in patients with diabetes.