This study investigated peptide changes and their bioactive functions through the long-term ripening of Gouda. Young Gouda (YG), medium Gouda (MG), and extra-sharp Gouda (EG) water extracts were prepared and functional peptides were recognized using liquid chromatography–high-resolution mass spectrometry. Two peptides with ACE-inhibitory effects (IQP and LQP) were identified in YG, while in MG and EG were identified eight (EL, IVP, VP, LPP, VIP, IPP, VPP, and VVPP) and six (EL, YL, VP, IR, YPEL, and DKIHPF) functional peptides, respectively. MG (70.26%) and EG (46.81%) showed stronger antioxidant activity than YG (25.99%) in ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) inhibition, though the DPPH (2,2-diphenyl-1-picrylhydrazyl) inhibition rate decreased with ripening. The antihypertensive effect increased in MG (79.76%) and EG (94.50%) due to ACE-inhibitory peptides. Measurements of inflammatory mRNA expression levels and immunoblotting were conducted to assess the anti-inflammatory properties. MG and EG suppressed the transcription of IL-1β and IL-6 mRNA. Immunoblotting indicated that EG suppressed IκBα phosphorylation to 57%. The enhancement of bioactive function in the water-soluble part of long-term ripened Gouda cheese may have affected identified peptides as well as unknown peptides. Further studies are expected to aid in discovering these novel bioactive peptides.