Along with the continuously advanced requirements for high performance rubbers such as in aircraft tires, natural rubbers show limitations in achieving high temperature creep resistance and high mechanical strength simultaneously. Meanwhile, the bi-terminal interactions of natural rubber (NR) exhibit unique reinforcement effects, which are difficult to realize in synthetic rubbers. In this article, four different types of bi-terminal polyisoprenes with distinct groups were synthesized, and they were assembled with penta-alanine molecule (5 A) to obtain high-performance rubbers by terminal hydrogen bonding reinforcement. Infrared tests indicate that the strong hydrogen bonds can be formed between two terminals and turn stronger after adding 5 A. Thus, the network of rubbers remains stable under different strains and temperatures and the activation energy of networks is elevated. As a result, this biomimetic design endows polyisoprene with high tensile strength compared with Malaysian NR and greater creep resistance. Further Mooney fitting and DMA test suggests that these confined hydrogen bonds not only increased the number of crosslinking points and entanglements of network, but also are beneficial for the segmental chain motion. In contrast to our common sense on hydrogen bonds which present large relaxation and hysteresis, this study proposes a facile method for preparing high-temperature creep-resistant rubbers by introducing confined hydrogen bonds, which represents a great advance in the structural biomimicry of NR.