A response surface methodology was used to optimise the solubilisation and precipitation of proteins from the cyanobacterium Arthrospira platensis. Two separate experiments were designed and conducted in a sequential manner. Protein solubilisation was affected by pH, extraction time, and biomass to solvent ratio (p < 0.001). Although spray-drying and the osmotic shock suffered when resuspending the dried biomass into distilled water led to a certain degree of cell wall disruption, the amount of protein that could be solubilised without an additional disruption step was in the range 30−60%. Sequential extractions improved protein solubilisation by less than 5%. For this reason, a pre-treatment based on sonication (400 W, 24 kHz, 2 min) had to be used, allowing the solubilisation of 96.2% of total proteins. Protein precipitation was affected by both pH and extraction time (p < 0.001). The optimised precipitation conditions, which were pH 3.89 over 45 min, led to a protein recovery of 75.2%. The protein content of the extract was close to 80%, which could be further increased by using different purification steps. The proteins extracted could be used in the food industry as technofunctional ingredients or as a source of bioactive hydrolysates and peptides for functional foods and nutraceuticals.