<p>Agave plants are used as ornamental plants or for alcoholic beverage production, leaving the leaves as agro-industrial waste, usually disposed of in the soil, causing acidification. On the other hand, type 2 diabetes mellitus (T2DM) affects more than 5&#xa0;million people worldwide and one route of treatment is through the inhibition of α-amylase and/or α-glucosidase. This work studied the infusions of fresh leaves of 13 <i>Agave</i> species available in the Valles Centrales and Mixteca regions of Oaxaca, Mexico. The content of total phenolic compounds, the antioxidant capacity, and the inhibitory activity of the enzymes α-amylase and α-glucoside in vitro, through a bioautographic assay and UV-vis, were analyzed. The results showed that all <i>Agave</i> species evaluated contain phenolic compounds with antioxidant activity, which is evidenced by the strong correlation between the phenolic compound content and the antiradical activity (r² &gt; 0.8481) determined by DPPH and for electron-donating capacity (r² &gt; 0.7088) measured by CUPRAC. The secondary metabolites in the agave leaf infusions showed low α-amylase inhibition, except that from <i>A. kerchovei</i>. The inhibition of α-glucosidase was superior to acarbose except for infusions from <i>A. stricta</i>, <i>A. kerchovei</i>, <i>A. angustiarum</i>, and <i>A. titanota</i>. Therefore, agave leaves represent an alternative source of antioxidants and bioactive compounds with the in vitro ability to inhibit the α-glucosidase enzyme, avoiding the secondary effects of acarbose because of the low α-amylase inhibition, contributing to the search for new drugs to combat T2DM, providing alternative uses for ornamental <i>Agave</i> species, and reevaluating the waste generated in the mezcal industry.</p>