Methanolic (M), hydroxymethanolic (AQ: M) and aqueous (AQ) fruit peel extract of Annona squamosa and Annona reticulata were investigated for their therapeutic potential. For this purpose, the total phenolic content, total flavonoid content and free radical scavenging activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric ion reducing antioxidant power (FRAP) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays were studied. Methanolic fruit peel extract of A. squamosa and A. reticulata showed highest total phenolic content (27.990.33 mgGAE/g dry material) and total flavonoid content (9.000.20 mgQE/g dry material), respectively. DPPH, ABTS and FRAP result indicated high antioxidant potential of fruit peel waste. This is the first report on GC-MS analysis of methanolic fruit peel extract of Annona and the results revealed the presence of three main therapeutically important bioactive compounds viz β-Pimaric acid, Spathulenol and 4H-Pyran-4-one in both the species with concentration of 24.32, 14.65 and 7.92%, respectively in A. squamosa and 18.58, 9.53 and 12.13%, respectively in A. reticulata. These compounds are reported to show antioxidant, antibacterial, antiproliferative, anticancerous, anti-inflammatory and immunomodulatory activities. Other compounds detected in these extract were n-Hexadecanoic acid (6.05%), n-Heptacosane (6.0%), 1H-Napthol[2,1-b]pyran-7-carboxylic acid, 3-ethenyldodecahydro-3,4a,7, 10a-tetramethyl-methyl ester (14.17%), 1,2-Benzenediol (8.33%) and 9,12-Octadecadienoic acid (ZZ)-(7.83%). The present report indicates a strong possibility of effective utilization of fruit peel waste for extraction of active principles.