Edible sweet potato leaf can be exploited in the management and treatment of insulin resistance. This study investigated the effects of three sweet potato leaf extracts (SPLEs) and chlorogenic acid (CGA) on glucose uptake (2-NBDG uptake and GLUT4 abundance) and expression of their related regulatory factors (such as IR, IRS-1, p-Akt1, and p-AMPKα1 abundances) using Western blot analysis in insulin-treated insulin-resistant C2C12 cells. The results show that both purple and green SPLEs improved glucose (2-NBDG) uptake efficacy with insulin treatments, and both SPLEs also increased GLUT4 and IR abundances via activation of p-Akt in the PI3K/Akt pathway, whereas the IR abundance efficacy influence was the same as in the insulin-treated group. The yellow SPLE and CGA have higher protein abundances of IR and IRS-1, while CGA (20 μg/mL) exhibits the highest abundance of p-Akt1 and p-AMPKα1. These results suggest potential benefits of purple and green SPLEs in promoting glucose uptake, possibly through modulation of insulin signaling pathways.