This study aimed to improve the industrial utility of defatted perilla seed residue (DPSR), a byproduct of perilla oil extraction. To maximize the release of DPSR's bioactive compounds, we prepared extracts using single or combined treatments of protease, cellulase, and pectinase, and then evaluated their physicochemical properties and antioxidant activities. All enzyme treatments significantly increased the content of soluble solids and reducing sugars compared to the control, with pectinase treatment yielding the highest sugar content. The pH values of all enzyme-treated groups were lower than the control. Regarding antioxidant components, groups treated with protease demonstrated exceptional efficiency. Ascorbic acid and total polyphenol content were most effectively extracted with protease alone, while the highest flavonoid content was achieved through complex enzyme treatment. The increase in these bioactive components directly correlated with improved radical scavenging activities. Specifically, a mixture of protease and cellulase exhibited the most potent DPPH and ABTS radical scavenging activities. Correlation analysis revealed a strong positive relationship between antioxidant components and activity indices, with a notably high correlation coefficient of 0.9684 between polyphenol content and ascorbic acid.