The carotenoids have vast medical, industrial, dietary, and pharmaceutical importance due to their provitamin A precursor, immunomodulator, antioxidant and photoprotective activity. The purpose of the research was to optimize the production of carotenoids using Rhodotorula mucilaginosa from artichoke agroindustrial waste as a low-cost substrate. The artichokes bracts waste was bleached by sodium hypochlorite (NaClO 2%) and was characterized through whiteness index and FTIR. The bleached artichoke waste (BABW) used in the fermentation went through acid hydrolysis, applying 8% of the bleached artichokes residue and sulfuric acid (2.5%) for 1 h at 90°C, obtaining a greater reduced sugars content at 3.1 g/L. Rhodotorula mucilaginosa was isolated and molecularly identified. The production of carotenoids from a culture media based on hydrolyzed BABW, peptone (0.5%), yeast extract (0.1%) and sodium chloride (0.5%) was evaluated at different conditions of pH (5–8) and agitation speed (80–160 rpm) applying the surface response methodology by a rotational central compound design. The best carotenoids performance obtained had 2968.95 µg/L VVC and 1228.53 µg/g TFC at pH 5, 120 rpm and 30°C for 72 h. The chemical characterization of the extracted carotenoids was confirmed by UV-VIS and Raman spectroscopy methods. The results suggest that Rhodotorula mucilaginosa is capable of producing carotenoids from artichoke waste fermentation, providing a low-cost and sustainable alternative route for use in the global market.