Metabolomic analysis provides critical insights into predator-prey interactions, yet the specific metabolites mediating predation strategies and defensive responses across distinct interaction stages remain poorly characterized. Using LC-MS/MS metabolomics, we investigated dynamic metabolic changes in a model intertidal predator-prey system-dogwhelks (Reishia clavigera) and mussels (Mytilus galloprovincialis)-across four predation stages: isolated in separate water (IS), same water without contact (SW), first touch (FT), and touch sustained over 3 h (T3h). Metabolomics results indicated that stage-specific metabolic reprogramming was observed. During the SW vs. IS comparison, dogwhelks upregulated steroid hormone biosynthesis and cysteine/methionine metabolism, producing differentially expressed metabolites (DEMs) such as Endomorphin-1. Conversely, mussels activated arachidonic acid metabolism and purine metabolism, triggering inflammatory responses and impaired stress regulation. At SW proximity without contact, dogwhelks mobilized energy and synthesized predatory toxins, while mussels exhibited metabolic signatures of inflammation and dysregulated self-control. Following physical contact (FT stage), dogwhelks elevated 5-Hydroxy-L-tryptophan (a serotonin precursor), ADP, and Trichloroacetic acid (a shell-dissolving agent), whereas mussels upregulated tryptophan metabolism, alongside stress-alleviating metabolites like Oxybuprocaine and Metamizole. After sustained predation (T3h), dogwhelks prioritized purine metabolism to meet their energy demands, while mussels activated tryptophan metabolism to produce adrenosterone (enhancing muscle mass) and metamizole (an analgesic), suggesting adaptive strategies to mitigate predation trauma. Besides, we conducted experiments on immersed angiotensin and found that it could influence the predation of dogwhelks. These results reveal divergent physiological strategies between predators and preys: dogwhelks optimize energy metabolism and toxin production to sustain predation, while mussels deploy stress-related metabolites, muscle-enhancing compounds, and pain-suppressing agents to resist capture. This study advances our understanding of predator-prey dynamics by linking metabolomic shifts to behavioral and physiological adaptations across interaction stages.