<p>The present study aimed to obtain polysaccharides from <i>Callisia repens</i> with anti-tyrosinase activity, sun protection factor (SPF), and antioxidant activity. Polysaccharides from <i>C. repens</i> were extracted using a citric acid-aspartic acid deep eutectic solvent (DES)-microwave-assisted approach, and the conditions (i.e., microwave power of 180 W, time of 4&#xa0;min, and DES concentration of 3%) were optimized using the Box–Behnken design to maximize tyrosinase inhibitory activity, SPF, and antioxidant activity. The responses obtained were: (a) monophenolase inhibitory activity = 98.8%, (b) diphenolase inhibitory activity = 81.6%, (c) 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging activity = 84.7%, (d) SPF = 6.05, and (e) yield = 7.2%. The extracted polysaccharides were then characterized. Low protein content indicated a high purity of the extracted polysaccharides. The infrared spectrum showed the functional groups of polysaccharides which indicate that polysaccharide has been successfully extracted. Monosaccharide analysis showed that it was mainly composed of glucose, galactose, and arabinose. Gel permeation chromatography (GPC) analysis indicated that it had a low molecular weight of 22.3 ± 0.3&#xa0;kDa. Based on copper chelating and ultraviolet–visible (UV–Vis) spectral analyses as well as kinetic study, it was suggested that the activities were contributed by this crude polysaccharide extract, which were found to be competitive inhibitors of tyrosinase. IC₅₀ values of 0.67 and 2.80&#xa0;mg/mL for monophenolase and diphenolase inhibitory activities were also obtained. Based on these results, structure–property relationships were confirmed, and the polysaccharides could be used in cosmetic applications.</p> Graphical Abstract <p></p>