Antarctica　is　the　coldest,　driest,　and　most　windy　continent　on　earth.　The　major　terrestrial　vegetation　consists　of　cryptogams　(mosses　and　lichens)　and　two　vascular　plant　species.　However,　the　molecular　mechanism　of　cold　tolerance　and　relevant　regulatory　networks　were　largely　unknown　in　these　Antarctic　plants.　Here,　we　investigated　the　global　alterations　in　metabolites　and　regulatory　pathways　of　an　Antarctic　moss　(Pohlia　nutans)　under　cold　stress　using　an　integrated　multi-omics　approach.　We　found　that　proline　content　and　several　antioxidant　enzyme　activities　were　significantly　increased　in　P.　nutans　under　cold　stress,　but　the　contents　of　chlorophyll　and　total　flavonoids　were　markedly　decreased.　A　total　of　559　metabolites　were　detected　using　ultra　high-performance　liquid　chromatography/electrospray　ionization　tandem　mass　spectrometry　(HPLC-ESI-MS/MS).　We　observed　39　and　71　differentially　changed　metabolites　(DCMs)　after　24　h　and　60　h　cold　stress,　indicating　that　several　major　pathways　were　differentially　activated　for　producing　fatty　acids,　alkaloids,　flavonoids,　terpenoids,　and　phenolic　acids.　In　addition,　the　quantitative　transcriptome　sequencing　was　conducted　to　uncover　the　global　transcriptional　profiles　of　P.　nutans　under　cold　stress.　The　representative　differentially　expressed　genes　(DEGs)　were　identified　and　summarized　to　the　function　including　Ca2+　signaling,　ABA　signaling,　jasmonate　signaling,　fatty　acids　biosynthesis,　flavonoid　biosynthesis,　and　other　biological　processes.　The　integrated　dataset　analyses　of　metabolome　and　transcriptome　revealed　that　jasmonate　signaling,　auxin　signaling,　very-long-chain　fatty　acids　and　flavonoid　biosynthesis　pathways　might　contribute　to　P.　nutans　acclimating　to　cold　stress.　Overall,　these　observations　provide　insight　into　Antarctic　moss　adaptations　to　polar　habitats　and　the　impact　of　global　climate　change　on　Antarctic　plants.　Copyright　©　2022　Liu,　Li,　Fang,　Zhang,　Yi,　Cong,　Zhang　and　Zhao.