In the present study, the effects of ultrasound (10, 20, and 30 min) on the bioactive compounds, antioxidant capacity, enzymatic inhibition, and in vitro digestion of six honey extracts from the Oaxaca state, Mexico, were analyzed. Significant differences were found in each honey extract with respect to the ultrasonic treatment applied (p < 0.05). In the honey extract P-A1 treated with 20 min of ultrasound, the phenols reached a maximum concentration of 29.91 ± 1.56 mg EQ/100 g, and the flavonoids of 1.92 ± 0.01 mg EQ/100 g; in addition, an inhibition of α-amylase of 37.14 ± 0.09% was noted. There were also differences in the phases of intestinal and gastric digestion, presenting a decrease in phenols (3.92 ± 0.042 mg EQ/100 g), flavonoids (0.61 ± 0.17 mg EAG/100 mg), antioxidant capacity (8.89 ± 0.56 mg EAG/100 mg), and amylase inhibition (9.59 ± 1.38%). The results obtained from this study indicate that, in some honeys, the processing method could increase the concentration of bioactive compounds, the antioxidant capacity, and the enzymatic inhibition; however, when subjected to in vitro digestion, the properties of honey are modified. The results obtained could aid in the development of these compounds for use in traditional medicine as a natural source of bioactive compounds.