The vast interconnection of resource-constrained devices and the immense amount of data exchange in the Internet of Things (IoT) environment resulted in the resurgence of various security threats. This resource-constrained environment of IoT makes data security a very challenging task. Recent trends in integrating lightweight cryptographic algorithms have significantly improved data security in the IoT without affecting performance. The PRESENT block cipher, a standard and lightweight benchmark algorithm, is a widely accepted and implemented algorithm with a simple design, low-cost implementation, and optimum performance. However, this simple design utilizing lightweight linear and non-linear functions led to slow confusion and diffusion properties. The static bits in the permutation layer are the leading cause of slow diffusion, showcasing dependencies between plaintext and ciphertext bits. This research addresses and seeks to overcome this shortcoming of slow confusion and diffusion using the Deoxyribonucleic Acid (DNA) replication process and shift-aided operations, leading to the DNA-PRESENT block cipher. Security, cost, and performance analyses were performed to verify the improvements. The results demonstrated that with only 33.5% additional cost, DNA-PRESENT increased key sensitivity to 73.57%, plaintext sensitivity to 33%, and consistently ensured an average bit error rate (BER) of 50.2%. An evident increase of 176.47 kb/s in throughput and reduced latency to 17 cycles/block kept the good hardware efficiency of 43.41 kbps/KGE, and the reduction in execution time by 0.2333 s led to better performance. Considering the security advances achieved, this cost increase is a trade-off between security and performance.