Durio zibethinus Murray, or durian fruit, is considered the “King of fruit” in various parts of Southeast Asia. It is classified in the Durio genus, which has been reported to be beneficial in the medical and pharmaceutical industry. The objective of this study was to investigate the physicochemical properties, biological activities, and cosmetic applications of the polysaccharide extractions from the green (GH) and white (WH) fruit-hulls and the ethanolic extracts from the pulp (P) and seeds (S) of D. Zibethinus. The extracts were developed as cosmetic products, and skin irritation was assessed by volunteers. P, S, GH, and WH extracts gave percentage yields of 12.13, 4.01, 1.60, and 1.18, respectively. The morphological structure of GH was highly porous, while the surface of WH was flattened, with no porosity observed. The seed extract showed the highest total phenolic content and antioxidant activity (DPPH) of 0.33 ± 0.01 mg GAE/g and IC50 0.08 ± 0.00 mg/mL, respectively, while no anti-tyrosinase activity was detected in any individual extract. The total phenolic content, DPPH assay, and anti-tyrosinase activity after blending the extracts were significantly (p < 0.05) higher than in the individual extracts. Combining extracts such as SGH and SGWH gave IC50 values of anti-tyrosinase activity at 8.69 ± 1.82 mg/mL and 0.067 ± 0.00 mg/mL, respectively. No durian extracts exhibited growth inhibition against Staphylococcus aureus, Streptococcus pyogenes, and Cutibacterium acnes. A gel formulation containing durian extract was prepared by a cold process. It had good stability, with no skin irritation reported by the volunteers. Both crude durian and polysaccharide extracts showed promise as active ingredients in cosmetic products.
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