Objective Genetic and environmental factors have important roles in the development of periodontitis. We aimed to assess the relation of vitamin D receptor (VDR) ApaI and TaqI polymorphisms and the susceptibility of periodontitis in Saudi population in Makkah region. Materials and Methods In total, 86 unrelated patients with moderate-to-severe periodontitis and 86 controls were enrolled in this study. Evaluation of the periodontal state was performed by using plaque index, bleeding on probing, probing depth, and attachment loss. Extraction of genomic DNA from peripheral blood and genotyping of VDR gene ApaI G/T (rs7975232) and TaqI T/C (rs731236) polymorphisms were performed by utilizing polymerase chain reaction and restriction digestion. Results There were statistically significant differences between both groups regarding the mean bleeding on probing, mean probing depth, mean plaque index, and the mean attachment level (p < 0.001) indicating that the matching based on the investigated groups was adequate. The examined populations were in Hardy-Weinberg equilibrium. Analysis of the genotype and allele frequencies of both VDR ApaI and TaqI single nucleotide polymorphisms revealed that they were statistically indifferent between the control group and the periodontitis subjects (p> 0.05). Conclusion These results suggested that VDR ApaI and TaqI polymorphisms might not be related to the susceptibility of periodontal disease in the Saudi subjects in Makkah region.