Abstract: Obesity is closely associated with a variety of metabolic diseases, including hyperlipidemia, atherosclerosis, and type 2 diabetes mellitus. Pancreatic lipase plays a critical role in the conversion of dietary lipids into triglycerides and free fatty acids, and the effective inhibition of its activity has emerged as a key therapeutic strategy for obesity management. This article systematically elucidates the principles, advantages, limitations, research progress, and influencing factors of several screening methods for pancreatic lipase inhibitors, including free enzyme-based assays, immobilized enzyme-based assays, and virtual screening. Furthermore, it offers a perspective on a multi-dimensional integrated screening paradigm characterized by "virtual screening-enrichment via immobilized enzymes-validation with free enzymes, " with the aim of providing valuable insights for the development of efficient and low-toxicity pancreatic lipase inhibitors.