This study was undertaken to uncover peptides from yeast extract that can enhance the perception of saltiness and to explore their effects on saltiness enhancement. Utilizing nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis, we identified peptides present in yeast extract. Through a virtual screening strategy, we selected fourteen candidate peptides with potential to enhance saltiness, along with two arginyl dipeptides. Molecular docking indicated that these peptides primarily interact with salt taste receptors via hydrogen bonding, with key binding sites identified as Arg583, Glu 326, and Tyr487, Arg491 for the taste receptors TMC4 and TRPV1, respectively. Sensory evaluation demonstrated that the saltiness-enhancing peptides (ADWPR, GDVDPF, NVDPF, WPEMDAL, LR, and VR) not only intensified the saltiness of a 0.30 % sodium chloride (NaCl) solution but also extended the duration of the saltiness sensation. Sigmoid curve analysis confirmed that these peptides could either synergistically or additively boost the saltiness of the salt solution. Interestingly, ADWPR and WPEMDAL were observed to reduce and moderate the saltiness intensity in high-concentration NaCl solutions, indicating a bidirectional regulatory effect. These findings reveal the potential mechanisms by which yeast extract can modulate saltiness and lay the groundwork for developing strategies to reduce salt content in food products, potentially leading to healthier dietary options.