ObjectivesPeri‐implantitis (PI) is the most common biological issue surrounding dental implants. According to current knowledge, the aforementioned complication is not equally distributed across different populations, and gene polymorphisms might be one contributing factor. The current study aimed to examine the association between gene polymorphisms of matrix metalloproteinase‐ (MMP‐) 1, ‐2, ‐3, ‐7, and ‐13 with PI in an Iranian demographic.Material and MethodsThe study's sample included 50 subjects suffering from PI and 89 healthy controls. From each participant, a venous blood sample of 5 cc was obtained, and DNA was extracted. Gene polymorphisms were investigated using restriction fragment length polymorphism polymerase chain reaction (RFLP‐PCR) combined with electrophoresis. Statistical analyses were done using the Pearson chi‐square test, odds ratio, and t‐test via SPSS version 28.ResultsThe MMP‐3 (‐1171 5A/6A) and MMP‐7 (‐181 A/G) gene polymorphisms were significantly different between the patients with PI and healthy controls (PV < 0.001 and =0.025, respectively). MMP‐1 (‐1607 1G/2G), MMP‐2 (‐1306 C/T), and MMP‐13 (‐77 A/G) gene polymorphisms did not, however, differ in terms of prevalence between the two groups (PV > 0.05). Moreover, the presence of the 6 A allele in the MMP‐3 (‐1171 5A/6A) genotype resulted in a significant decrease in PI risk (PV < 0.001).ConclusionsGene polymorphisms in the genotypes of MMP‐3 (‐1171 5A/6A) and MMP‐7 (‐181 A/G) were differential when comparing PI patients and healthy controls of the studied population.