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Objective: The aim of this systematic review was to provide evidence related to the association between non-antiresorptive medications and MRONJ. Materials and methods: The following three electronic databases were screened: PubMed, EMBASE, and Web of Science from December 2020 until April 2021. Two reviewers independently performed the study selection, data extraction, and quality assessment of the included studies. The Newcastle–Ottawa Scale (NOS) was used for assessing the risk of bias. A meta-analysis was performed for assessing the relationship between MRONJ and non-antiresorptive medications. Results: The search strategy retrieved 996 articles. Following removal of duplicates, title, and abstract screening and full-text reading, 58 publications were eligible to be included in the review. A total of 867 cases of MRONJ were included (33% female, 55% male, 12% no gender reported). The mean age of the patients when MRONJ was diagnosed was 61 years (range 19–100 years) and the average time of diagnosis was 10 months following non-antiresorptive drug therapy. Patients with a history of corticosteroids (0.61, 95% CI 0.39, 0.82, p = < 0.001) and chemotherapy (0.59, 95% CI 0.51, 0.67, p = < 0.001) showed the highest significant effect size (ED) compared to the control group for MRONJ occurrence. Conclusion: A significant association existed between MRONJ and non-antiresorptive drugs. However, considering limited evidence, findings should be interpreted with caution. Clinical relevance: The non-antiresorptive drugs might allow the dentist to apply the principle of "drug holiday" following concurrence from the drug prescribing clinician. Prospero registration number: CRD42020173891. [ABSTRACT FROM AUTHOR]