Phycocyanin (PC) is a blue protein pigment whose interest increased due to its potential as alternative to synthetic food colorants. The cyanobacteria of the genus spp. are the main source of commercially available PC. The extraction and purification processes showed high variability in yield, purity, quality and environmental and economic sustainability. During the last years, different extraction methods like freezing and thawing, ultrasound assisted extraction and enzyme assisted extraction have been improved to increase PC yield and reduce purification steps once crude extract is obtained. This review aims to provide a comprehensive analysis of PC extraction techniques from biomass. Conventional and innovative technologies are compared to highlight their performances, in terms of yield, purity, feasibility, cost, and environmental impact. Furthermore, separation and purification are reported to elucidate which processes are adopted nowadays and which are the possible improvement to increase the purity grade of protein. This comparative study also aims to provide the basis for the development of alternative methods for the optimization of phycocyanin extraction, using also neural networks and artificial intelligence.