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Current trends are shifting attention to the sustainable valorization of food bio-waste management and by-product utilization, as they are rich in nutrients and bioactive compounds, such as dietary fiber, polyphenols, and peptides. Upcycled ingredients and green cosmetics are becoming more and more appealing concepts in the nutraceutical and cosmetic industries encouraging them to invest and develop sustainable products aligning with the green concept of circular economy. In this research, we focused on the waste products (peels) of super exotic fruits Litchi chinensis and Selenicereus undatus, which are packed with antioxidants, fibers, vitamins, and minerals. Extraction of the peels with green solvent (propylene glycol) was performed and optimized by the means of an I-optimal and box-behnken designs with different independent variables for each design and total phenolic content (TPC) as a response. The resulted optimized extract of lychee peels propylene glycol extract (LPPG) was evaluated in terms of anti-tyrosinase activity, resulting in an (IC50 = 264.1 ± 16.9 µg/mL) with an average inhibition percentage of (92.33%), DPPH assay was performed, revealing antioxidant activity of (2666.7 ± 68.71 µmol ascorbic acid/mL) and (24,774.68 ± 834.67 µmol ascorbic acid/mL) using ABTS assay. As for dried dragonfruit propylene glycol extract (DDPG), the antioxidant activity was found to be (1299.82 ± 20.80 µmol Ascorbic acid/mL) using DPPH assay and (1510.506 ± 12.93 µmol Ascorbic acid/mL) using ABTS assay. In conclusion, optimization of the extraction process of food by-products using propylene glycol as a solvent may offer a valuable sustainable cosmetic ingredient. [ABSTRACT FROM AUTHOR]