Extremophilic proteins are valuable in various fields, but their expression can be challenging in traditional hosts like due to misfolding and aggregation. (), a halophilic expression system, offers a solution. This study examined cleavable and non-cleavable purification tags at both the N- and C-termini when fused with the superfolder green fluorescent protein (sfGFP) in . Our findings reveal that an N-terminal 8xHis-tag or Strep-tagII significantly enhances protein production, purity, and yield in . Further experiments with mCherry and halophilic alcohol dehydrogenase (ADH) showed improved expression and purification yields when the 8xHis-tag or Strep-tagII was positioned at the C-terminus for mCherry and at the N-terminus for ADH. Co-positioning 8xHis-tag and Twin-Strep-tag at the N-terminus of sfGFP, mCherry, and ADH yielded significantly enhanced results. These findings highlight the importance of thoughtful purification tag design and selection in , providing valuable insights for improving protein production and purification with the potential to advance biotechnological applications.