A processor manages memory-mapped input/output (MMIO) accesses, in secure fashion, at an input/output memory management unit (IOMMU). The processor is configured to ensure that, for a given MMIO request issued by a processor core and associated with a particular executing VM, the request is targeted to a MMIO address that has been assigned to the VM by a security module (e.g., a security co-processor). The processor thus prevents a malicious entity from accessing confidential information of a VM via MMIO requests.