This study aimed to investigate the influence of polysaccharides extracted from sesame seed hulls using ultrasound-assisted alkaline extraction techniques on the inhibition of α-amylase and α-glucosidase activities. Polysaccharides from sesame hulls, with a yield of 6.49%, were separated into three distinct fractions using column chromatography. These fractions were then analyzed for their primary components and their potential to lower blood sugar levels. The major fraction, Pol-1, accounting for 1.74% of the total, contained components such as rhamnose (9.3%), glucose (9.2%), glucuronic acid (14.1%), and galacturonic acid (50.4%), along with other constituents. Our results revealed that varying concentrations of these polysaccharide fractions significantly influenced the reduction of glucose diffusion and the inhibition of both α-amylase and α-glucosidase activities. Notably, Pol-1 exhibited the most substantial inhibitory effects on both enzyme activities, as well as a notable decrease in glucose diffusion rate. These effects have the potential to extend the blood glucose response and regulate postprandial glucose levels. Consequently, sesame seed hull polysaccharide fractions hold promise for improving blood glucose regulation and could find applications in functional foods.