| Summary: | The root bark of <i>Morus alba</i> L. (Mori Cortex) is used to treat diuresis and diabetes in Chinese traditional medicine. We evaluated different solvent extracts and bioactive components from the root bark of <i>Morus alba</i> L. for their antioxidant, anti-α-glucosidase, antityrosinase, and anti-inflammatory activities. Acetone extract showed potent antioxidant activity, with SC<sub>50</sub> values of 242.33 ± 15.78 and 129.28 ± 10.53 µg/mL in DPPH and ABTS radical scavenging assays, respectively. Acetone and ethyl acetate extracts exhibited the strongest anti-<i>α</i>-glucosidase activity, with IC<sub>50</sub> values of 3.87 ± 1.95 and 5.80 ± 2.29 μg/mL, respectively. In the antityrosinase assay, the acetone extract showed excellent activity, with an IC<sub>50</sub> value of 7.95 ± 1.54 μg/mL. In the anti-inflammatory test, ethyl acetate and acetone extracts showed significant anti-nitric oxide (NO) activity, with IC<sub>50</sub> values of 10.81 ± 1.41 and 12.00 ± 1.32 μg/mL, respectively. The content of the active compounds in the solvent extracts was examined and compared by HPLC analysis. Six active compounds were isolated and evaluated for their antioxidant, anti-<i>α</i>-glucosidase, antityrosinase, and anti-inflammatory properties. Morin (<b>1</b>) and oxyresveratrol (<b>3</b>) exhibited effective antioxidant activities in DPPH and ABTS radical scavenging assays. Additionally, oxyresveratrol (<b>3</b>) and kuwanon H (<b>6</b>) showed the highest antityrosinase and anti-α-glucosidase activities among all isolates. Morusin (<b>2</b>) demonstrated more significant anti-NO and anti-iNOS activities than the positive control, quercetin. Our study suggests that the active extracts and components from root bark of <i>Morus alba</i> should be further investigated as promising candidates for the treatment or prevention of oxidative stress-related diseases, hyperglycemia, and pigmentation disorders.
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