Information security is one of the foundational requirements for any modern society thriving on digital connectivity. At present, information security is accomplished either through software algorithms or hardware protocols. Software algorithms use pseudo random numbers generated by one-way mathematical functions that are computationally robust in the classical era, but are shown to become vulnerable in the post-quantum era. Hardware security overcomes such limitations through physically unclonable functions (PUFs) that exploit manufacturing process variations in the physical microstructures of Si integrated circuits to obtain true random numbers. However, recent upsurge in reverse engineering strategies make Si-PUFs vulnerable to various attacks. Moreover, Si-PUFs are low-entropy, power-hungry, and area-inefficient. Here we introduce a biological PUF which exploits the inherent randomness found in the colonized populations of T cells and is difficult to reverse engineer and at the same time is high-entropy, non-volatile, reconfigurable, ultra-low-power, low-cost, and environment friendly.