After harvesting cherimoya fruit, the trees release huge amounts of leaves, which are burned by farmers. This work shows that the leaves can be used as a source of antioxidants. Total phenolic compounds (TPC) and antioxidant activity (AA) of extracts of the dry leaf of Annona cherimola Mill in 70% v/v ethanol, water at 80 °C, subcritical water (SW) at 110 °C, 120 °C and 130 °C were determined, following a factorial design with the Minitab program. The TPC was quantified with the Folin Ciocalteu methodology, and the AA with 2,2-diphenyl-1-picrilhidrazil (DPPH) and Ferric Reducing Antioxidant Power (FRAP). Results indicate that the type of solvent and the extraction time had a significant effect on the TPC and AA of the extracts. Extracts of cherimoya leaves were found to be a potential antioxidant. The extract of SW at 130 °C presented the highest content of TPC (5.6 g EAG/100 g dry leaves) and the ethanolic extract had the highest AA (0.86 mg trolox equivalent/mg dry extract, IC50 = 0.020 mg dry extract/mL extract of dry leaves and FRAP of 1710.14 µmol ET/g dry leaves) and the extracts obtained with SW at a lower temperature presented a higher AA value.