With　global　enforcement　of　plastic　bans　and　restrictions,　the　biodegradable　plastic,　e.g.,　polylactic　acid　(PLA),　has　been　extensively　employed　as　a　primary　substitute　for　traditional　petroleum-based　plastics.　However,　the　growing　problem　associated　with　PLA　waste　accumulation　is　posing　grand　environmental　challenges.　In　addition,　although　PLA　has　the　degrading　property　under　natural　conditions,　the　degradation　process　takes　too　long　and　the　degradation　products　cannot　be　recycled.　In　this　context,　enzymatic　degradation　of　PLA　arouses　great　attention　in　scientific　communities.　This　study　aims　at　selecting　the　most　cost-effective　protease　from　various　enzymes　and　optimizing　the　enzymolysis　conditions　towards　the　degradation　of　PLA.　We　will　demonstrate　that　under　an　optimal　temperature　of　45　degrees　C,　a　pH　vale　of　11,　and　an　enzyme　concentration　of　0.6　mg　mL(-1),　the　protease　K　would　achieve　a　remarkable　degradation　efficiency　(＞　99　%)　for　PLA　films　within　just　50　min.　Finally,　molecular　dynamics　(MD)　simulation　and　molecular　docking　studies　reveal　the　mechanism　behind　the　protease　induced　PLA　degradation,　providing　a　promising　direction　for　waste　treatment　and　resource　utilization　for　future　biodegradable　plastics.