The leaves of Aerva lanata are one of the indigenous medicinal plants used in the management of diabetes mellitus and its associated complications in Africa. However, its effect on the activities of diabetes-related enzymes has not been investigated. This study evaluated the in vitro inhibitory effects of different extracts of the A. lanata leaf on the activities of diabetes-related enzymes (α-amylase and α-glucosidase) and chemically induced free radicals. Aqueous, ethanol, and hydroethanol extracts of A. lanata leaves were subjected to a standard enzyme inhibition assay followed by determination of modes of inhibition of the enzymes. The antioxidant activities of the extracts were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The results obtained showed that the hydroethanol extract of the A. lanata leaf optimally inhibited both α-amylase (IC50: 2.42 mg/mL) and α-glucosidase (IC50: 0.23 mg/mL). The Lineweaver-Burk plot revealed that the mode of inhibition of both enzymes by the hydroethanol extract was uncompetitive. However, the hydroethanol and aqueous extracts displayed the best DPPH and ABTS radical-scavenging ability, respectively. It can be concluded that the A. lanata extract inhibited the activities of both α-amylase and α-glucosidase uncompetitively, which may be attributed to its free radical-scavenging properties and rich phenolic composition.