The incidence of diabetes is on the rise and one of the medically active plants used for the treatment of diabetes in South Africa is Lauridia tetragona. The aim of this study is to investigate the antidiabetic property of the polyphenolics (PP) compounds isolated from the methanolic extract of Lauridia tetragona. The α-amylase, α-glucosidase, dipeptidyl peptidase IV (DPPIV), lipase inhibitory activities, and glucose uptake in HepG2 were investigated. The methanolic extract fractions of L. tetragona yielded six fractions (PP1−PP6) all of which showed weak inhibition against DPPIV and lipase compared to the standards. However, PP4 and PP6 showed the best inhibition against α-amylase (IC50 of 359.3 ± 2.11 and 416.82 ± 2.58 μg/mL, respectively) and α-glucosidase (IC50 of 95.93 ± 2.34 and 104.49 ± 2.21 μg/mL, respectively) and only PP4 (173.6%) resulted in enhanced glucose uptake in HepG2 cells compared to berberine (129.89%) and metformin (187.16%) used as positive controls. The previous investigation on PP4 and PP6 showed the presence of polyphenolics such as ferulic acid, coumaric acid, and caffeic acid. The results of this study suggest that L. tetragona could be suitable as an antidiabetic agent and justifies the folkloric use of the plant to treat diabetes.