Arsenic (As) contamination in agricultural water and soil poses a growing threat to leafy vegetable safety, with lettuce being particularly vulnerable due to its high water content and direct consumption without processing. This study investigated the capacity of exogenous syringic acid (SyA) to mitigate As-induced toxicity in lettuce plants, integrating physiological, biochemical, and untargeted metabolomics approaches. Arsenic significantly reduced plant biomass (31% and 53% in fresh and dry weight), impaired stomatal conductance, and suppressed net CO2 assimilation. However, the SyA application, particularly at 10 μM, significantly restored biomass, photosynthetic performance, and redox homeostasis under As stress. Notably, SyA enhanced antioxidant capacity, as reflected by elevated FRAP and CUPRAC activities and increased accumulation of the phenolic compounds. Untargeted metabolomics revealed that As exposure broadly reprogrammed secondary metabolism, including activation of the phenylpropanoid and shikimate pathways with notable accumulation of flavonoid glycosides and alkaloids, consistent with a shift toward oxidative defense. Conversely, SyA at 500 μM exerted phytotoxic effects even under nonstress conditions, confirming a biphasic, concentration-dependent mode of action with a critical threshold between 250 and 500 μM. The findings suggest that an optimized concentration of SyA can act as a metabolic modulator, fine-tuning the plant responses to As by boosting the antioxidant defense system.