This study evaluated the potential in vitro inhibitory activity of Basella alba leaves against enzyme markers of diabetes mellitus, α-amylase, and α-glucosidase. The dried plant sample was ground into fine powder, defatted, and soaked in methanol to obtain the crude extract. The crude methanolic extract of Basella alba was then fractionated sequentially in acetone-methanol mixtures with increasing solvent polarity ratios. Fractions obtained were evaluated for their α-amylase and α-glucosidase inhibitory potential. The standard drug, acarbose inhibited 37.44 ± 7.65%, 83.99 ± 0.86%, and 86.52 ± 0.40% of α-amylase activity at 10, 30, and 50 ppm. The highest inhibition was observed in the acetone-methanol (4:1) fraction which inhibited 57.80 ± 0.71%, 56.39 ± 0.49%, and 46.94 ± 0.26% of α-amylase activity, followed by the acetone fraction with inhibitory activity of 22.24 ± 0.41%, 38.05 ± 0.68%, and 46.62 ± 0.32% at increasing concentrations of 50, 200, and 350 ppm, respectively. The acetone-methanol (1:4) mixture exhibited the lowest activity at 8.00 ± 0.35% for 50 ppm, and 0.61 ± 0.27% for 200 ppm. However, no inhibitory activity was demonstrated in any of the fractions of Basella alba against α-glucosidase. Total flavonoid content analysis revealed that all fractions have the same flavonoid content. Basella alba may serve an essential role in managing the risk of diabetes mellitus and is recommended for consumption on a regular basis....