Luke and Alex School Safety Act of 2021 This bill requires the Department of Homeland Security (DHS) to establish a Federal Clearinghouse on School Safety Best Practices for use by state and local educational and law-enforcement agencies, institutions of higher education, health professionals, and the public. The bill requires DHS to collect clearinghouse data analytics, user feedback on the implementation of best practices and recommendations identified by the clearinghouse, and any evaluations conducted on these best practices and recommendations. In addition, DHS must coordinate with the Departments of Education, Health and Human Services, and Justice to assess and identify best practices and recommendations and establish an advisory board to provide feedback and propose additional recommendations. Further, the bill specifies the criteria for best practices and recommendations of the clearinghouse, including evidence that the best practice or recommendation has had a significant effect on improving the health, safety, and welfare of individuals in school settings. Finally, the bill provides for grant program review.