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Tyrosinase is the key enzyme in the production of melanin. Tyrosinase inhibitors have gained interest in the cosmetics industry to prevent hyperpigmentation and skin-related disorders by inhibiting melanin production. It has been reported that several Aloe species exhibit anti-tyrosinase efficacy in vitro. In this study, the exudates of thirty-nine South African Aloe species were screened to identify species and compounds with anti-tyrosinase activity. Qualitative screening revealed that twenty-nine Aloe species exhibited tyrosinase inhibition activity with one to three active bands. Quantitative screening was performed for 29 species and expressed as IC 50 values. Three species were further analysed and subsequently, aloesin and aloeresin A was isolated from A. ferox and plicataloside from A. plicatilis and A. chabaudii. Aloeresin A was determined to be a substrate of mushroom tyrosinase. Dose-response assays showed that aloesin (IC 50  = 31.5 μM) and plicataloside (IC 50  = 84.1 μM) exhibited moderate to weak activity. Molecular docking scores for plicataloside were considerably lower than for aloesin (P < 0.01), confirming its lower IC 50 . Several Aloe species may have potential for the management of hyperpigmentation or as a skin lightening agent. This is the first report showing that plicataloside, present in A. plicatilis and A. chabaudii, exhibits anti-tyrosinase activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)