Peptides were compounds with intermediate molecular structures between amino acids and proteins, having numerous nutritional properties including easy absorption, low osmotic pressure, low immunogenicity, and high tissue permeability. They were also important chemical messengers for tissue and cells capable of regulating cellular metabolism. Food-derived peptides were an important nutritional bases prepared from food protein using either a restriction enzymatic hydrolysis or biological fermentation, possessing both good nutritional value and exerting various physiological modulatory activities. However, the transport and absorption of food-derived functional peptides, as well as the spatial and temporal dynamic distribution in intracellular subcellular organelles and its functional effect on the regulation of nutrient metabolism, have yet to be studied. Moreover, the mode of action of the synergy between different structural and functional peptide molecules (such as transmembrane peptides, signal peptides, transport peptides, etc.) remained unclear, thereby restricting the basic research and rapid industrial development of food-derived peptides. Herein, the multi-dimensional peptide function evaluation methods in chemical, in vitro biological, lower/higher model animals, and clinical dimensions as well as the molecular structure-activity relationships of food-derived peptides were systematically introduced. The molecular conformational rules of food-derived peptides were described from the “top-down” and “bottom-up” approaches, and a “structure-effect” characterization theory based on molecular hybridization orbitals had been developed. Furthermore, the structure-activity relationship of peptide molecules with different molecular and structural features (such as primary amino acid sequence, spatial configuration, arrangement of the peptide bonds in the main chain, diversity of side chain functional groups, and α-carbon chirality, among others, etc.) in the process of transport and absorption had also been reviewed. The regulative law of body metabolism by food-derived peptides in complex systems of nutrition research field and the scientific underpinnings of peptide absorption and metabolism, and its ramifications for regulating precision nutrition, have also been examined. The functional properties of food-derived peptides, the “structure-activity” relationship, and the absorption and metabolism mechanism were all described in detail in order to provide some scientific guidance and reference for the future research on food-derived peptides.