The present disclosure provides an information handling system (IHS) and related methods that provide secure shared memory access (SMA) to shared memory locations within a Peripheral Component Interconnect (PCI) device of an IHS. The IHS and methods disclosed herein provide secure SMA to one or more operating system (OS) applications that are granted access to the shared memory. According to one embodiment, the disclosed method provides secure SMA to one or more OS applications by receiving a secure runtime request from at least one OS application to access shared memory locations within a PCI device, authenticating the secure runtime request received from the OS application, creating a secure session for communicating with the OS application, and providing the OS application secure runtime access to the shared memory locations within the PCI device.