Manganese (Mn) plays an essential role in plant growth; however, excessive Mn is toxic to plants. Polygonum lapathifolium Linn. was tested as a novel Mn-hyperaccumulating species in our previous study, but the underlying mechanisms of this hyperaccumulation are poorly understood. A hydroponic experiment with (8 mmol L−1) and without additional Mn (CK) was established to explore the possible mechanisms through the effects on photosynthesis-related physiological characteristics and metabolomics. The results showed that additional Mn increased plant biomass, photosynthesis, and stomatal conductance related to increases in the effective photochemical quantum yield of photosystem II and relative electron transport rate (P < 0.05). The results from liquid chromatography–mass spectrometry revealed 56 metabolites differentially accumulated between the plants composing these two groups. Metabolites were enriched in 20 metabolic pathways at three levels (environmental information processing, genetic information processing, and metabolism), of which five metabolic pathways were associated with significant or extremely significant changes (P < 0.05). These five enriched pathways were ABC transporters (environmental information processing), aminoacyl-tRNA biosynthesis (genetic information processing), biosynthesis of amino acids, d-arginine and d-ornithine metabolism, and arginine biosynthesis (metabolism). Flavonoids may play a key role in Mn tolerance, as they accumulated more than 490-fold, and the relationship between flavonoids and Mn tolerance needs to be studied in the future.