Background: Silkworm cocoons are rich in bioactive compounds beneficial for cosmetic applications. This study presented a novel approach by comparing microwave and ultrasonic pretreatments to enhance silk protein extraction efficiency. The aim was to evaluate the effects of pretreatment methods and extraction solvents on the bioactive components, physicochemical properties, and biological activities of silkworm cocoon extracts for cosmetic applications. Methods: Cocoons of Bombyx mori (Nang Lai) were pretreated using conventional soaking (12 h), microwave (3 min), or ultrasonication (30 min), and then subjected to aqueous or enzymatic extraction. The extracts were analyzed for protein, phenolic, and flavonoid content. Structural and thermal properties were characterized using infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Antioxidant and anti-aging properties were assessed by measuring the inhibition of nitric oxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH^•), and collagenase. Skin moisturizing effects and irritation potential were tested. Results: Silkworm cocoons pretreated with microwave (ALM) and ultrasonication (ALS), followed by enzymatic extraction, had the highest yields (21.6 ± 0.5% and 21.7 ± 0.4%, respectively). Despite their slightly lower protein contents, these extracts showed elevated phenolic and flavonoid content. ALM and ALS demonstrated strong antioxidant activities, with DPPH^• scavenging of 65.9 ± 0.2% and 65.2 ± 0.3%, collagenase inhibition of 60.3 ± 0.8% and 59.7 ± 1.7%, and nitric oxide inhibition of 13.5 ± 0.4% and 12.9 ± 0.2%, respectively. Skin moisturizing effects increased by 63.6 ± 2.1% for ALM and 61.2 ± 1.5% for ALS, compared to 1.3 ± 0.6% in the control. All extracts were found to be non-irritating for topical application, indicating their safety for skincare formulations. Conclusions: Microwave and ultrasonication pretreatments, in combination with enzymatic extraction, provide an effective, time-efficient, and sustainable method for producing silkworm cocoon extracts with promising cosmetic applications.