Turmeric (Curcuma longa L.) is known for its health benefits. Several previous studies revealed that curcumin, the main active compound in turmeric, has antioxidant capacity. It has been previously demonstrated that puffing, the physical processing using high heat and pressure, of turmeric increases the antioxidant and anti-inflammatory activities by increasing phenolic compounds in the extract. The current study sought to determine if high hydrostatic pressure extraction (HHPE), a non-thermal extraction at over 100 MPa, aids in the chemical changes and antioxidant functioning of turmeric. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) analyses were conducted and assessed the content of total phenol compounds in the extract. The chemical changes of curcuminoids were also determined by high performance liquid chromatography (HPLC). Among the three variables of ethanol concentration, pressure level, and treatment time, ethanol concentration was the most influential factor for the HHPE of turmeric. HHPE at 400 MPa for 20 min with 70% EtOH was the optimal extraction condition for the highest antioxidant activity. Compositional analysis revealed that 2-methoxy-4-vinylphenol was produced by puffing. Vanillic acid and ferulic acid content increased with increasing HHPE time. Synergistic effect was not observed on antioxidant activity when the turmeric was sequentially processed using puffing and HHPE.