Effective removal of drilling-mud filter cake during well completion is essential to reduce the formation damage caused by drilling activities in many production and injection wells. This task is very difficult to achieve, especially in horizontal/multilateral wells. Harsh chemical treatments (acids, oxidizers, and chelating agents) have been used extensively to conduct water-based mudcake cleanup treatments. However, these approaches have been limited due to the associated high corrosion rates and un-even mudcake removal. With their controlled reaction with the mudcake, mild chemical nature, better health, safety and environmental (HSE) profile, enzymes provide an excellent alternative to harsh chemical treatments in high temperature formations. However, their use has been limited to relatively low temperature applications due to their instability at elevated temperature values.In this work, two enzymatic systems were evaluated: old α-amylase system and new structurally reinforced α-Helix system. The old enzyme was found to form a potentially damaging precipitate at reservoir temperature above 100 o C. The degree of this damage was assessed using size-matching technique and core-flood experiments. This potential of secondary formation damage was drastically reduced in the new improved enzyme system. Enzyme denaturing was minimized by protecting the catalytic center using preferential hydration of proteins with a Polyol.The effectiveness of the new system was proven in the lab through comparative tests. Bioassay by reducing sugar estimation showed better biopolymer hydrolyzing capability of the new system at higher temperatures. In contrast to old enzyme system, core-flood experiments, conducted at high temperatures, using new enzyme system, showed the enzyme denaturing did not occur and the core oil permeability increased at stabilized pressure. In addition, this paper will also highlight the advantages and disadvantages of each enzyme system in terms of stability, compatibility, and mudcake damage reversal.