Vitamin D has anti-proliferative, anti-inflammatory, and apoptotic abilities. Vitamin D deficiency can induce deoxyribonucleic acid (DNA) damage. The aim of the study was to create a systematic review to analyze the relationship between vitamin D and DNA damage in various populations. PubMed, Scopus, EbscoHost, Google Scholar, and Epistemonikos were used to identify literature regarding the relationship between vitamin D and DNA damage. Assessment of study quality was carried out by three independent reviewers individually. A total of 25 studies were assessed as eligible and included in our study. Twelve studies were conducted in humans consisting of two studies with experimental design and ten studies with observational pattern. Meanwhile, thirteen studies were conducted in animals (in vivo). It is found that the majority of studies demonstrated that vitamin D prevents DNA damage and minimizes the impact of DNA damage that has occurred (p<0.05). However, two studies (8%) did not find such an association and one research only found a specific association in the cord blood, not in maternal blood. Vitamin D has a protective effect against DNA damage. A diet rich in vitamin D and vitamin D supplementation is recommended to prevent DNA damage.