Advances　in　technological　and　bioinformatics　approaches　have　led　to　the　generation　of　a　plethora　of　human　gut　metagenomic　datasets.　Metabolomics　has　also　provided　substantial　data　regarding　the　small　metabolites　produced　and　modified　by　the　microbiota.　Comparatively,　the　microbial　enzymes　mediating　the　transformation　of　metabolites　have　not　been　intensively　investigated.　Here,　we　discuss　the　recent　efforts　and　technologies　used　for　discovering　and　mining　enzymes　from　the　human　gut　microbiota.　The　wealth　of　knowledge　on　metabolites,　reactions,　genome　sequences,　and　structures　of　proteins,　may　drive　the　development　of　strategies　for　enzyme　mining.　Ongoing　efforts　to　annotate　gut　microbiota　enzymes　will　explain　catalytic　mechanisms　that　may　guide　the　clinical　applications　of　the　gut　microbiome　for　diagnostic　and　therapeutic　purposes.　©　2021　Elsevier　Ltd