“Horchata” is a well-known Spanish beverage obtained from pressing tiger nuts. Its by-product is a potential source of sugar and fiber but also contains polyphenols; thus, it could be used as a new ingredient in the food industry. The aim of this work is to determine the phenolic compounds and compare the phenolic profile of two tiger nut by-products. A Box–Behnken design has been carried out to optimize the extraction of phenolic compounds from tiger nut by-products by ultrasound technology. The independent factors were time (min), ethanol/water (% v/v), and solvent/sample ratio (v/w). The model was validated and confirmed by ANOVA. A Protected Designation of Origin (PDO) of Valencia and a non-Protected Designation of Origin (n-PDO) tiger nut by-products were extracted under the optimal conditions and were characterized by HPLC-DAD-ESI-TOF-MS (High Performance Liquid Chropatography coupled to a photodiode array time-of-flight mass detector). Moreover, their antioxidant activities measured by three different methods (DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-Azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt) and FRAP (ferric reducing antioxidant power)) were compared. A total of 45 polar compounds were identified, and the phenolic ones were quantified, some of them for the first time. PDO tiger nut by-product has been demonstrated to be richer in phenolic acids and other polyphenols and has higher antioxidant activity; meanwhile, n-PDO tiger nut by-product is richer in phenol precursors.