Background: Improved adherence to oral anti-hyperglycemic drugs (OAHs) may improve glucose control while also lowering diabetes morbidity, mortality, and long-term health resource consumption. Aim: This study aims to compare the adherence of type 2 diabetes mellitus (T2DM) patients to sulfonylureas with metformin. Methods: This systematic review and meta-analysis followed the PRISMA 2020 guidelines. A systematic search was done in PubMed, MEDLINE through Clarivate, Web of Science through Clarivate, and EBSCO. Studies retrieved were managed in Rayyan–Intelligent systematic reviews website for duplicate removal and screening. Review Manager 5.4 was used to generate forest plots to estimate pooled odds ratios using a random-effect model. We used the Higgin's I2 test for assessing between-study heterogeneity. We used funnel plots for assessment of publication bias. Results: This review included data from 11 studies on 274,202 T2DM patients. Random effect meta-analysis revealed that the odds for higher proportion of adherence favoured sulfonylurea group (OR = 1.34, 95% CI [1.08-1.65]). The comparison between sulfonylurea and metformin adherence using OR was significant (p=0.007).  Conclusion: The study concludes that T2DM patients were significantly more adherent to sulfonylurea than metformin, however, the analysis showed significant heterogeneity. We recommend adherence measures to be devised when prescribing OHAs.