Background: The use of Aspirin in the primary prevention of cardiovascular disease (CVD) is still a topic of debate, especially in patients with diabetes. The present meta-analysis aims to rule out the efficacy of Aspirin in patients with diabetes and to compare the effectiveness of Aspirin with a placebo (or no treatment) for the primary prevention of CVD and all-cause mortality events in people with diabetes. Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using Aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received Aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. Results: A total of 5 studies out of 13 were included with 23,570 diabetic patients; 11,738 allocated to Aspirin and 11,832 allocated to the placebo group. In patients with diabetes, there was no difference between Aspirin and placebo with respect to the risk of all-cause death with a confidence interval (CI) varying 0.63 to 1.17. In addition, there were no differences in the bleeding outcomes with an odds ratio of 1.4411 (CI 0.47 to 4.34). Conclusion: Aspirin has no significant risk on primary endpoints of cardiovascular events and the bleeding outcomes in diabetic patients compared to placebo. More research on the use of Aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research.