Background: Blood group antigens play a critical role in transfusion medicine, affecting the safety and effectiveness of blood transfusions. Among these blood groups, the Kidd blood group system, which includes Jka, Jkb, and Jk3 antigens, is particularly significant due to its implications in delayed hemolytic transfusion reactions and its genetic variability across different populations. Objectives: This study compared the prevalence of Kidd blood group phenotypes among Saudi and non-Saudi blood donors in the regional blood bank in Riyadh, Saudi Arabia. The goals were to understand the distribution of these antigens and assess the level of genetic integration between the two groups. Methods: A cross-sectional study was conducted with 311 blood donors, comprising 155 Saudis and 156 non-Saudis. The phenotypes analyzed included Jk(a+b+), Jk(a-b+), Jk(a+b-), and Jk(a-b-). Data were collected from the regional blood bank in Riyadh, and statistical analysis was performed using Chi-square tests to compare phenotype distributions between the groups. Results: The study found that the most prevalent phenotype was Jk(a+b-), occurring in 47.74% of Saudis and 44.23% of non-Saudis. The least common phenotype was Jk(a-b-), observed in just over 1% of non-Saudis and less than 1% of Saudis. The prevalence rates for Jk(a+b+) and Jk(a-b+) were similar between the two groups, suggesting a high level of genetic integration. No significant differences were found in the distribution of these phenotypes between Saudi and non-Saudi donors, indicating substantial genetic similarity and intermingling. Conclusions: The results suggest that the regional blood bank in Riyadh has a homogenized population concerning Kidd blood group antigens, facilitating the development of donor databases that include comprehensive antigen profiles. These databases can enhance the precision of blood matching and reduce the risk of transfusion reactions. This study highlights the importance of genetic diversity in developing personalized medicine strategies and adapting transfusion protocols to local and regional antigen profiles.