C. vulgaris microalgae biomass was employed for the extraction of valuable bioactive compounds with deep eutectic-based solvents (DESs). Particularly, the Choline Chloride (ChCl) based DESs, ChCl:1,2 butanediol (1:4), ChCl:ethylene glycol (1:2), and ChCl:glycerol (1:2) mixed with water at 70/30 w/w ratio were used for that purpose. The extracts’ total carotenoid (TCC) and phenolic contents (TPC), as well as their antioxidant activity (IC50), were determined within the process of identification of the most efficient solvent. This screening procedure revealed ChCl:1,2 butanediol (1:4)/Hsub.2O 70/30 w/w as the most compelling solvent; thus, it was employed thereafter for the extraction process optimization. Three extraction parameters, i.e., solvent-to-biomass ratio, temperature, and time were studied regarding their impact on the extract’s TCC, TPC, and IC50. For the experimental design and process optimization, the statistical tool Response Surface Methodology was used. The resulting models’ predictive capacity was confirmed experimentally by carrying out two additional extractions under conditions different from the experimental design.