Techniques for multiplexing between an execute-in-place (XIP) mode and a memory-mapped input/output (MMIO) mode for access to external memory devices are described herein. In an example embodiment, an IC device comprises a serial interface and a controller that is configured to communicate with external memory devices over the serial interface. The controller comprises a control register and a cryptography block. The control register is configured to indicate an XIP mode or a MMIO mode. Caches in XIP interfaces provide seamless access to multiple memories, or multiple portions of a single memory. The cryptography block is configured to encrypt and decrypt XIP data transfers to and from a first external memory device in the XIP mode, and to encrypt and decrypt MMIO data transfers to and from a second external memory device in the MMIO mode.