Introduction: Adherence to oral antidiabetic treatment (OAHA) in patients with type 2 Diabetes mellitus (T2DM) is far from reaching the desirable figures. A multitude of studies have been published on factors that influence non-adherence, although with different populations and methodologies. Therefore, the aim of this systematic review was identify and collect those factors that may influence non-adherence to OAHAs treatment in patients with T2DM. Method: The databases used in the literature search were Medline (PubMed), Scopus, CINAHL and PsycINFO. We considered case-control studies, cohorts and randomised clinical trials conducted in people with T2DM and OAHA treatment, where determinants of adherence were evaluated. The review process was conducted independently by two investigators based on Prisma recommendations. Results: Of 11 publications selected, two were case-control studies and nine were cohort studies (seven retrospective). Non-adherence figures ranged from 20.3 to 48 %. Factors associated with non-adherence to OAHAs were found to be: patient co-payment, daily OAHA dose, type of OAHA prescribed, number of medications prescribed, less frequent appointments with healthcare staff, high HbA1C levels, depression, female sex, race/ethnicity (other than white), marital status (other than married) and age. Conclusions: From a clinical point of view, it is important to identify which risk factors are modifiable and thus, healthcare professionals will be able to design actions for patients to improve their adherence to OAHAs treatment as well as improve T2DM control.