With an ever-increasing globalization of the semiconductor chip manufacturing supply chain coupled with soaring complexity of modern-day integrated circuits (ICs), intellectual property (IP) piracy, reverse engineering, counterfeiting, and hardware trojan insertion have emerged as severe threats that have compromised the security of critical hardware components. Logic locking (LL) is an IP protection technique that can mitigate these threats by locking a given IC with a secret key. Earlier LL demonstrations based on traditional silicon complementary metal-oxide-semiconductor (CMOS) technology and emerging memristors require significant hardware investment in the form of additional input gates and extensive CMOS peripherals, rendering them area- and energy-inefficient. In this article, we demonstrate multiple two-dimensional (2D) nanoscale memtransistor-based programmable logic gates such as AND, NAND, OR, XOR, and NOT gates, each of which can be locked/unlocked without requiring peripherals and at minuscule energy expenditure (<1 pJ). We also show that SAT-solver is unsuccessful in breaking into any of the ISCAS’85 benchmark circuits that utilize our LL scheme. The massive resilience to SAT-attack is attributed to the prowess of programmable 2D memtransistors which enable device-level LL of all the gates in each of the benchmark circuits. Given that 2D transistors are drawing increasing attention of chip manufacturing corporations like Intel, TSMC, etc., to replace and/or augment silicon at aggressively scaled technology nodes, our demonstration of area- and energy-efficient LL can be considered as a step toward the realization of secure ICs enabled by 2D nanoscale memtransistors.