The effect of four different extraction methods on physicochemical characteristics and functionalities of chloro-phycocyanin (CP) was investigated. Swelling (S-CP), freezing and thawing (4FT-CP), ultrasonication with freezing and thawing (4FT+U-CP), and the high-pressure cell disruption (HPCD-CP) process affected CP differently, thus resulting in different levels of solubility, DPPH scavenging activity, ABTS scavenging activity, and reducing power. Among the four CPs, HPCD-CP had the highest CP content (15.3%), purity (1.66 ± 0.16), and ∆E value but the lowest ∆b value. The ζ potential of HPCD-CP (−38.8 mV) was the highest, but the average particle size of 4FT+U-CP (719.1 nm) was the highest. UV-Vis absorption spectra and fluorescence spectra illustrated that high-pressure cell disruption-assisted extraction had more profound impacts on the microenvironment of tetrapyrrole chromophores, the environment of aromatic amino acids, and the phycocyanobilin of CP. Furthermore, HPCD-CP and 4FT-CP showed higher solubility and antioxidant activities than S-CP, especially 4FT+U-CP. The results obtained in this study demonstrate that HPCD technology could obtain a food-grade C-phycocyanin product with higher CP concentration, purity, solubility, and antioxidant activity.