Background Primary prevention of type 2 diabetes mellitus (T2DM) is possible in at-risk populations, and prevention programmes have been shown to be effective in real-world scenarios. Despite this evidence, diabetes prevalence has tripled in recent decades and is expected to reach 700 million patients by 2045, making it one of the leading causes of death globally. This review is aimed at identifying the issues and challenges in the primary prevention of T2DM. Methods Scopus, Web of Science, PubMed and Ovid MEDLINE were systematically searched for published articles. Articles were screened based of inclusion and exclusion criteria. The inclusion criteria were: (1) published in 2010-2020, (2) full original article, (3) written in English, (4) qualitative, mixed-methods article, observational or interventional study. The exclusion criteria were: (1) animal study, (2) in vivo/in vitro study, (3) type 1 diabetes or gestational DM and (4) conference abstract, book chapter, report, and systematic review. Eligible articles were assessed using Mixed Methods Appraisal Tool (MMAT) by three assessors. Results A total of 11 articles were selected for qualitative synthesis from the initial 620 articles. The issues and challenges seen in T2DM primary prevention followed three themes: healthcare program (sub-themes: lack of resources, community partnership, participation, health literacy), health provider (sub-themes: lack of implementation, health care staff, collaboration, availability), individual (sub-themes: awareness, communication, misbehaviour, family conflict). Conclusion Factors relating to healthcare programmes, health providers, and individual issues are the main challenges in T2DM primary prevention. By establishing sustainable preventative initiatives that address these issues and challenges in the primary prevention of T2DM, a reduction in T2DM prevalence could be achievable.