Litchi chinensis Sonn. (litchi) pericarp, a major byproduct of litchi processing, is rich in bioactive polysaccharides; however, the structure-bioactivity relationship has not been well studied. Here, a homogenous polysaccharide LPPs-1 was isolated and purified from litchi pericarp, having a weight-average molecular weight of 38.97 kDa (polydispersity index <1.6) and containing the following 9 monosaccharides: L-rhamnose, D-galacturonic acid, D-galactose, L-arabinose, d-glucose, D-xylose, D-mannose, L-fucose, and D-glucuronic acid in a 3.84: 18.55: 13.77: 28.01: 14.06: 9.42: 10.10: 1.18: 1.06 M ratio. NMR spectroscopy identified a → 4)-α-D-GalpA-(1→, →3,6)-β-D-Galp-(1→, and →5)-α-L Araf-(1 → backbone, in a 22.03: 14.06: 10.74 M ratio. Notably, LPPs-1 reversibly inhibited α-amylase (hybrid) and α-glucosidase (uncompetitive) (IC50s: 0.16 mg/mL and 0.24 mg/mL, respectively). The dual enzyme-inhibitory effect of LPPs-1 suggests its potential as a naturally occurring hypoglycemic agent. Our findings indicate the potential of litchi pericarp polysaccharides as a functional food in the management of diabetes.