The disclosed systems, structures, and methods are directed to a computer system including a PCIe protection controller as a part of a PCIe root complex that includes at least one root port. Each root port is configured to optionally connect to at least one endpoint device, and each endpoint device is designated as a secure endpoint device or a nonsecure endpoint device. The PCIe protection controller is configured to control outbound traffic to protect secure endpoint devices from access from any nonsecure components of the computer system. The PCIe protection controller may be further configured to control inbound traffic to prevent access to secure memory by nonsecure endpoint devices. The PCIe protection controller may be dynamically configured at runtime to designate endpoint devices as either secure or nonsecure.